Greg has stayed under the radar throughout high school with one friend, Earl, playing video games, avoiding Earl's scary brothers, and making terrible movies for fun. Greg's mother gets the idea that Greg should befriend a girl named Rachel, who has leukemia. Against Greg's better judgment and despite his social awkwardness, he does. When Rachel makes the decision to stop leukemia treatment, Greg and Earl must abandon invisibility and make a stand for friendship and compassion.