With a fifteenth season already in the works, Grey’s Anatomy is on track to eclipse ER as the longest-running primetime medical drama in TV history. While the show has never regained the hype it experienced during the early days, Grey’s still pulls in an impressive audience year after year — continually making it one of the most profitable shows on television.

Of course, you don’t make it to 300 episodes without your fair share of turnover.

While Ellen Pompeo continues to play the titular character of Meredith Grey, the cast of Grey’s Anatomy has been in a constant state of flux ever since the show began. In fact, only three main cast members aside from Pompeo have remained since the show's debut, with many of the other actors leaving willingly or having their characters meet an unfortunate end.

While the series has certainly contained its fair share of drama in the last fourteen years, what keeps many people engaged in Grey's is the behind-the-scenes happenings that have often changed the direction of the show. While many actors have praised Shonda Rhimes for her compassion, others have publicly been at odds with the series creator, resulting in their characters being written off.

Let's take a look at Where Are They Now: The Departed Cast Of Grey’s Anatomy.

14. Eric Dane - Mark Sloan

After working as a professional actor since the early ‘90s, Eric Dane landed his breakout role as Dr. Mark Sloan in season two of Grey’s Anatomy. He became a series regular from seasons three through eight, until Mark met his tragic end following a plane crash, which also claimed the life of his girlfriend, Lexie Grey. The hospital was eventually retitled the Grey-Sloan Memorial Hospital in the midst of their loss.

Dane’s exit from the show was something the actor worked with series creator Shonda Rhimes to develop, as they wanted to give Mark the send-off he deserved. Then, just a month later, it was announced that Dane would star as the lead in the upcoming TNT action series The Last Ship, which debuted in the summer of 2014. Dane will reprise his character of Admiral Tom Chandler in the fifth and final season of the show, which is expected out later this year.

Just as many viewers had become fixated on Dr. Mark Sloan's love life on Grey's, many were upset to hear that Dane and his wife of 14 years, Rebbecca Gayheart, had separated early this year, citing irreconcilable differences. The two had recently appeared together in the 2017 thriller Grey Lady before news of their split made headlines.

13. Sandra Oh - Cristina Yang

Sandra Oh made her debut as Cristina Yang in the pilot episode of the series and continued to play the surgical intern who worked her way up to cardiothoracic surgeon throughout the first ten seasons of the show. Although she originally auditioned to play Miranda Bailey, Oh was eventually given the part of Cristina, which earn the actress critical praise. She won a Golden Globe in 2006 for her performance and was nominated for Outstanding Supporting Actress in a Drama Series at the Primetime Emmys five years in a row.

Oh left the show toward the end of season ten when her character was offered to run a newly established hospital in Switzerland by her former fiancé, Preston Burke.

Since her departure, Oh has graduated from supporting character to leading lady.

The 46-year-old Canadian actress currently plays the lead character of Eve Polastri on BBC America's Killing Eve. The series, which is based on the Villanelle novel series by Luke Jennings, finds Oh portraying an M15 officer who becomes obsessed with tracking down an infamous assassin.

Killing Eve has once again earned Oh critical acclaim, achieving a 100% approval rating on Rotten Tomatoes and earning the series a second season — indicating that Oh may have yet another hit on her hands.

12. T. R. Knight - George O'Malley

T. R. Knight first debut as George O’Malley on the pilot episode of the series, where he played one of the five surgical interns alongside Meredith Grey.

Knight ended his time on the show after feeling as though his character was getting overlooked throughout the season five storyline.

This behind-the-scenes controversy first began when co-star Isaiah Washington was accused of using a homophobic slur against Knight, which resulted in Knight deciding to publicly come out as gay. Knight felt as though Shonda Rhimes had tried to discourage him from coming out, which he believed may have been the reason his part was being reduced the following season. This lead to one of the most bizarre departures from the series, in which Knight’s character decides to inexplicably join the Army before he is hit by a bus.

However, leaving the show doesn’t seem to have hindered Knight’s acting career, as he’s shown up in a number of critically acclaimed TV shows and movies since, including The Good Wife, 11.22.63, and the Jackie Robinson biopic 42.

More recently, Knight has appeared on the National Geographic anthology series Genius, where he has undergone an impressive transformation to portrayed former FBI-director J. Edgar Hoover. He also re-teamed with Rhimes on The Catch.

15. Sara Ramirez - Callie Torres

Sara Ramirez has had one of the longest character arcs on Grey's Anatomy, appearing in over 10 seasons and 200 episodes of the show as Dr. Callie Torres. She first popped up as the senior orthopedic resident in season two of the show before she became a series regular in season three and beyond. Ramirez was nominated for a number of awards for her performance, which was praised for its realistic depiction of a bi character — a community which the actress is also a proud member of.

Ramirez parted ways from the series amicably -- with her character leaving Seattle to start a new life for herself in New York -- as the actress wanted to take some time off from the show and explore new opportunities in Hollywood.

Since she left the series in 2016, Ramirez has continued to provide her voice for the character of Queen Miranda on the popular Disney animated series Sofia the First.

More recently, Ramirez joined the cast of Madam Secretary as a series regular. The show just wrapped up its fourth season with a fifth already in the works, where Ramirez is expected to reprise her role as Kat Sandoval, the newest policy advisor to the series protagonist, Elizabeth McCord.

11. Kate Walsh

Kate Walsh made her debut in the season one finale of Grey’s, where her character was originally conceived to have a short-lived run that was meant to throw a wrench into the relationship developing between Meredith and her estranged husband, Derek Shepherd.

However, Walsh’s performance as the willful Dr. Addison Mongomerty was so strong that the actress was turned into a series regular before she was eventually given the lead of her own spin-off series, Private Practice. She continued to guest star on Grey’s Anatomy during this time, but she hasn’t appeared on the series since season eight.

Since she’s completed work on both shows, Walsh has had quite the active career in Hollywood. In 2014, she appeared in the hit FX anthology crime series Fargo, where she played Gina Hess opposite Martin Freeman. Last year, she appeared in the R-rated comedy Girls Trip as well as the popular Netflix series 13 Reasons Why as series regular Olivia Baker.

Last year, the actress also disclosed that she was diagnosed with a brain tumor back in 2015. Fortunately, Walsh successfully had the tumor removed only a few days after her diagnosis, and it turned out to be benign. The actress ended up taking off work for a number of months to recover.   

10. Isaiah Washington - Preston Burke

Isaiah Washington’s sudden departure from the series was another instance where the behind-the-scenes drama seemed to eclipse the drama on the show.

The American actor played Dr. Preston Burke in the first three seasons, where his relationship with Cristina Yang served as one of the prominent story arcs. However, while shooting the third season Washington was accused of using a homophobic slur in regards to his co-star T. R. Knight while he was engaged in a fight with Patrick Dempsey. As a result, his contract was not renewed for the following season.

After leaving the show, Washington secured a role in the CW series The 100, where he appeared as Thelonious Jaha throughout the first five seasons of the show before the character met his demise.

Washinton has also appeared in a number of feature films since Grey's, including The Sinner Ser and Dead Trigger. He is set to star in the upcoming heist movie Cut Throat City, which takes place in New Orleans following the destruction of Hurricane Katrina.

Washington has three children together with Jenisa Marie Garland, his wife of over 20 years. The actor has also continued to donate and complete charity work in Sierra Leone ever since Washington discovered that the country was home to his ancestors.

9. Katherine Heigl - Izzie Stevens

Katherine Heigl’s departure from Grey’s in the middle of season six caused many to speculate that the actress was difficult to work with. These rumors began to circulate when Heigl publicly withdrew herself from the 2008 Emmy nominations, stating that her season four storyline was not strong enough for consideration — especially after winning the award for Outstanding Supporting Actress the year before.

This would have understandably irked series creator Shonda Rhimes, and Dr. Izzie Stevens was eventually written out of the show not long after. Heigl later apologized to Rhimes, and the actress has stated multiple times that she would be open to returning to the series to give her character the proper send off. However, Izzie has yet to make her return.

More recently, Heigl played the lead characters in the NBC series State of Affairs and the CBS series Doubt — both of which were canceled after their first season. She also starred in the 2017 thriller Unforgettable opposite Rosario Dawson.

Heigl is currently set to join the cast of Suits for the upcoming eighth season, where she will play the cutthroat attorney Samantha Wheeler, who is set on making partner before the year’s end. With stars Gina Torres, Meghan Markle, and Patrick J. Adams all departing the series, Suits is in need of some serious star power.

8. Jeffrey Dean Morgan - Denny Duquette

Though his time on the series was short-lived, Jeffrey Dean Morgan’s portrayal as Denny Duquette was certainly a memorable one as it came during the season two hype of the series — when Grey’s Anatomy was at its most watched.

Denny was a patient at Seattle Grace Hospital who was being treated for a lifelong heart condition. He developed a relationship with Izzie Stevens which ultimately led to the two getting engaged. However, he passed away following a heart transplant, leaving Izzie and the audience utterly heartbroken.

Morgan’s stardom has only continued to grow since his time on the medical drama.

Around the same time that he was winning over hearts playing Denny, Morgan appeared in the hit CW show Supernatural as well as the R-rated superhero movie Watchmen -- making him a favorite amongst sci-fi and fantasy nerds

More recently, he landed a recurring role in the hit legal drama The Good Wife before he was cast to play the ultimate villain, Negan, in AMC’s The Walking Dead. This sinister yet charismatic performance has earned Morgan the most notoriety to date, as Negan has proven to be the most menacing presence throughout the show's lengthy run. He is expected to reprise the character in the upcoming season.

6. Chyler Leigh - Lexie Grey

Chyler Leigh first popped up as Lexie Grey at the end of season three when she was spotted by Derek Shepherd at Joe’s Bar. The two have a flirtatious encounter similar to Derek’s first meeting with Meredith — though little does he know that the new girl is actually Meredith’s younger half-sister who been transferred to Seattle Grace Hospital.

Though Lexie was originally intended to have only a small character arc, Leigh was eventually made a series regular, appearing as a main cast member from seasons four to eight. She developed a relationship with Mark Sloan before Lexie met her demise following a plane crash. This corresponded with the actress's desire to be written out of the show so she could spend more time with her family.

Two years after her departure from the series, Leigh nabbed the leading role in the NBC series Taxi Brooklyn, where she played an NYPD detective who must partner up with a cab driver when her license is suspended. The action-comedy was canceled after just one season, though the actress has had better luck in recent years with her performance as Alex Danvers in the CW Arrowverse, where she is a series regular in Supergirl.

7. Brooke Smith - Erica Hahn

Brooke Smith first appeared as Dr. Erica Hahn in the second season of the show, where she was a cardiothoracic surgeon, workaholic, and longtime rival of Dr. Preston Burke. After Burke develops hand tremors, Dr. Hahn is transferred to Seattle Grace Hospital to work as his replacement, which made Smith a series regular throughout the fourth season of the show.

However, Smith was given the news that her character was going to be written out of the show in season five despite positive feedback from viewers. Smith believed that this sudden change of direction came from the studio executives, who may have been uncomfortable with the lesbian relationship that was developing between Erica and Callie on the show. This caused even more backlash from viewers, who felt as though the famously progressive show was being back-pedaled by the studio amidst surging popularity.

Fortunately, Smith has continued to have a steady stream of work in both TV and film.

She’s enjoyed recurring roles in Ray Donovan, Bosch, and Bates Motel, where she played Sheriff Jane Greene in season five of the show. Smith even popped up in a recent episode of Supergirl, reuniting her with her former Grey’s co-star Chyler Leigh.

5. Gaius Charles - Shane Ross

After receiving critical acclaim for his performance as Brian “Smash” Williams on Friday Night Lights, Gaius Charles returned to TV a few years later to play Dr. Shane Ross on Grey’s Anatomy. Shane was one of the new interns who was brought to Seattle Grace Hospital at the start of season nine, where he idolizes Derek Shepherd and dreams of becoming a surgeon.

Before the audience was ever really able to connect with the character, Charles left the show at the end of season eleven when he decided to follow Christina Yang to Switzerland to work at a newly established facility.

Though his time on Grey's may have been short-lived, the 35-year-old American actor has popped up in a number of successful shows and movies before and since. He briefly appeared as a CIA Officer in the 2010 Angelina Jolie movie Salt, right around the same time that he starred in the action movie Takers and the celebrated war drama The Messenger.

More recently, he appeared as Bunchy Carter, a Black Panther leader, in the NBC crime drama Aquarius before he secured a leading role in another NBC show, Taken, which was adapted from the Liam Neeson film series. Unfortunately, both shows were canceled after their second seasons.

4. Tessa Ferrer - Leah Murphy

One of the latest departures from the series, Tessa Ferrer did not return for season fourteen of the show as the surgical resident Leah Murphy. However, that’s not to say that Ferrer will never return to the series, as she was written out after Leah was deemed unfit to work as a surgeon.

Ferrer was originally cast in the role back in season nine, and much like the other residents, Murphy was a competitive workaholic -- though she was often insecure about her ability to work as a surgeon. After Murphy was fired from the hospital, Ferrer ended up reprising the character a couple of seasons later, as Leah had spent the intervening years refining her surgery skills at Foster Hospital before returning to Grey-Sloan.

Since she left the show just last year, Ferrer popped up in Insidious: The Last Key, which may not have been the most critically successful of the Insidious movies, but did end up becoming the highest-grossing film of the franchise.

Ferrer also has a number of other projects in the works, including a role in the upcoming TV series Catch-22, where she will star alongside a number of A-list actors, including George Clooney and Hugh Laurie.

3. Martin Henderson - Nathan Riggs

Though he is probably best known for starring in action movies — including Smokin’ Aces, Flyboys, and Everest — Martin Henderson joined the cast of Grey’s Anatomy for a two-season arc portraying the cardiothoracic surgeon Nathan Riggs.

The character debuted not long after Derek Shepherd met his demise on the series, and Martin eventually fires up a romantic relationship with Meredith Grey. However, the character’s storyline was never conceived to last more than a few seasons, and Henderson left the show when his character was reunited with his long-lost fiancee at the beginning of season fourteen.

Earlier this year, Henderson returned to the big screen with his performance in The Strangers: Prey at Night — a fitting project considering Henderson’s breakthrough role came with his performance in the 2002 adaptation of The Ring. The film found Henderson starring opposite Mad Men’s Christina Hendricks in the second installment of the horror series which went on to be a box office success.

The New Zealand actor is also set to star as the lead character in the upcoming film Hellbent, which centers on a teenage girl who embarks on a cross-country road trip alongside a criminal with the hopes of tracking down her estranged father.

2. Jerrika Hinton - Stephanie Edwards

Jerrika Hinton joined the cast as Stephanie Edwards in the ninth season of the show, where she played a surgical intern working under Meredith Grey. She was eventually upgraded to a series regular from seasons ten to thirteen, where she is involved in a love triangle with Jackson Avery and April Kepner.

She departed from the show during the season thirteen finale, where she suffers significant burns during a hospital fire. Having spent her childhood being treated for sickle-cell disease and her adult life working as a doctor, Stephanie comes to the conclusion that she doesn’t want to spend her entire life in hospitals and she sets out to see the world.

While a number of Grey’s cast members have departed from the series citing differences with creator Shonda Rhimes, Rhimes actually cast Hinton to play the lead character in Toast — a comedy series Rhimes was developing for ABC. After shooting the pilot, Toast was never ordered for a full series, and Hinton ended up leaving Grey’s the following year.

Since she left the series, Hinton was cast as one of the lead characters on the HBO series Here and Now.

Despite the talented creator Alan Ball (Six Feet Under, True Blood) and a cast headed up by Tim Robbins and Holly Hunter, the series was canceled after just one season.

1. Patrick Dempsey

Easily one of the biggest stars to come out of Grey’s Anatomy, Patrick Dempsy has continued to pop up in various TV shows and movies since he concluded his time on the series.

Dempsey first appeared in the pilot episode of Grey’s as Derek Shepherd, a neurosurgeon at Seattle Grace Hospital, who goes on to form a relationship with Meredith Grey. The two eventually marry and have three children together before Derek met his tragic demise following a car accident.

Although Dempsey still had time left on his contract following his character's passing, the actor and series creator Shonda Rhimes said that the character’s story came to a close organically — though that didn’t stop fans from angrily petitioning for the character’s return.

Dempsey concluded his time on the show in 2015, and the following year he popped up in the R-rated rom-com Bridget Jones’s Baby alongside Renee Zellweger and Colin Firth. Dempsey is currently set to star in the upcoming mini-series The Truth About the Harry Quebert Affair, where he will portray the title character.

On top of his successful acting career, Dempsey is also an avid auto racer.

He has competed in a number of pro-am races, including the Rolex 24 at Daytona and the 24 Hours of Le Mans. Dempsey has said he has even entertained the idea of dropping acting and focusing on motorsports full-time.

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Which departed Grey's Anatomy character do you miss the most? Let us know in the comments!