The Flare is that deadly, brain-eating disease that all of the Cranks have. It's, you know, the thing that's destroying the world. The Flare seems to be a kind of global pandemic, one so large and deadly that it actually unifies all of the nations of the world.
Thomas describes the Flare like this: "The Flare destroyed your brain, slowly driving you insane and stripping you of the capacity to feel basic human emotions like compassion or empathy" (11.5). Yeah, the Flare isn't much fun. The worst part about it may be that it doesn't directly kill you; it actually makes you worse than dead. It makes you inhuman, which is everyone's greatest nightmare.
And the worst worst part? "The Flare always wins in the end" (35.24).
Well, that's encouraging.
The Flare is what WICKED is fighting against. Somehow the Gladers, under WICKED's—ahem—"direction," are supposed to save the world. Logically, it seems that the Gladers' task is to destroy the Flare… or at least come up with some kind of cure for the whole world.
Basically, the world is sick, and these kids have to fix it.