Throughout Goku’s Dragon Ball career, he has faced a number of increasingly powerful threats, ones that have ranged from threatening to destroy the Earth to wiping out the entire universe–but out of all of them, only one stands above the rest as the all-time greatest threat Goku has ever faced as it was the only one that managed to kill the Saiyan permanently.
Goku was introduced in the first chapter of Dragon Ball, and right from the start, it was clear that this person was not to be messed with, even though he was just a little kid at the time. Just within the first few chapters, Goku took a bullet to the face with zero damage, brought down a powerful gang leader, and even toppled a world-wide fascist regime. As Goku defeated stronger and stronger villains, he, too, grew in strength to match them. Goku’s first truly magnificent metamorphosis of power was when Goku unlocked Super Saiyan for the first time while battling Frieza, but even that immensely strong transformation quickly became obsolete. Before long, Goku was reaching SSJ2 and SSJ3 without breaking a sweat until finally Goku transcended his mortal limitations and channeled the power of a god with Super Saiyan God, Super Saiyan Blue, and Ultra Instinct. Now, there is hardly a villain in the multiverse that can challenge Goku’s power–except one, which would have been able to kill him regardless of how powerful he became.
In Dragon Ball chapter 335 by Akira Toriyama, Goku is in the middle of a battle that would decide the fate of the entire world with Androids 19 and 20. While Goku was powered up to SSJ1 and ready to fight, he suddenly felt a sharp pain in his chest and started to lose energy rapidly–and then he remembered what Trunks told him about his alternate self in Trunks’ desolate future. In a previous chapter, Trunks traveled back in time to warn the Z Fighters of the impending threat of the Androids while also making some pretty drastic changes to the time stream while he was at it. In Trunks’ timeline, Goku died of a heart disease before he got the chance to fight the Androids, leaving the world incredibly vulnerable. Now, in this chapter, Goku’s destiny was coming to pass, and he was rounding the corner of death without the ability to throw a single punch in defense.
Goku is a fighter who only grows in strength the tougher a situation is, but in this case, the disease he suffered from simply killed him with no epic power up or chance for redemption. Without warning, reasoning, or prejudice, this virus takes Goku’s life without giving him any way to fight against it. For this reason, the heart virus is easily the greatest threat Goku has ever faced, even compared to the strongest fighters he’s gone up against throughout his career. Even Jiren gave Goku the chance to refine his Ultra Instinct power-up before trying to throw him out of the ring during the Tournament of Power, and he was arguably the strongest fighter in existence. No, this virus came silently and took Goku’s life quickly–a hauntingly humbling end to perhaps the most incredible martial artist in the known multiverse.
Luckily for the Goku of the prime Dragon Ball timeline, Trunks gave him the medicine he would need to beat his heart condition, he just didn’t take it before squaring off with the Androids because, well, no one ever claimed Goku was smart. However, in the end, he did survive the disease thanks to the assistance of a friend from the future. If it hadn’t been for that life-saving medicine, though, Goku would have ended up just like his alternate timeline counterpart–a version of Goku that confirms what his greatest threat in the Dragon Ball universe truly was.