The Last of Us has inspired some smart fan theories. As is often the case with most story-driven games, the narrative leads players to concoct their own elaborate explanations, even for elements of the story that weren't mysterious. From ideas that explain Ellie's past to possible crossovers from other video games, The Last of Us fan theories abound.
A big reason for all the fan theories is the moral ambiguity of the game. Joel, the hero, is forced into difficult situations where there's often no obvious answer. Players search for clues and reasons why things turned out the way they did. When there isn't an obvious one, they often come up with their own theories to fill in the holes in just the same way people invent conspiracy theories for confounding events in the real world.
Not every The Last of Us theory is perfectly sound. Some seem pretty ludicrous while others appear to be pretty likely, but that's just the nature of fan theories in a nutshell.
It should go without saying, but there are The Last of Us spoilers ahead.
According to the Fireflies, Ellie needs to die so they could dissect her brain and discover the cure. According to this theory, that's only partly true. The Fireflies could derive a cure from Ellie without murdering her, but as long as she is alive, other factions, such as the military, can do the same. By killing her and becoming the only ones with the cure, the Fireflies would become the most influential organization in the world.
When Joel and Ellie arrive, the Fireflies almost immediately decide that she must die in order to produce a cure. The problem is, all of their reasoning is very, very flawed. Instead of scientifically studying the only known immune person in existence, they immediately want to kill her without first running comprehensive diagnostics or tests. It's likely that even if they did kill Ellie, they wouldn't have the knowledge, ability, or patience to develop a cure from her brain.
Fans love to consider the possibility that some of their favorite games are playing out in the same universe. In this theory, The Last of Us and the Uncharted series take place a few decades apart on the same timeline. The idea is that Nathan Drake is indirectly responsible for the infection. In Uncharted 3, Drake foils a plot to find a sunken vessel with what is essentially an ancient chemical weapon in it.
If Drake failed, the villainous Marlowe would have uncovered the vessel and perhaps unleashed the Cordyceps virus on the world of The Last of Us. The chronology could work, but this Uncharted 4 newspaper Easter egg is the only real evidence of a shared universe.
When you think about all the stuff that Joel has gone through, this theory makes a lot of sense. In addition to spending a lot of time with the infected Ellie, he's also constantly coming into contact with other afflicted folks. He fights them hand-to-hand on an all-too regular basis, yet he somehow manages to avoid it himself. Either he is incredibly lucky, or he's immune. If he is immune, there's a question of whether or not he's aware of it.