Seventeen-year-old Greg has managed to become part of every social group at his Pittsburgh high school without having any friends, but his life changes when his mother forces him to befriend Rachel, a girl he once knew in Hebrew school who has leukemia. Greg's life is one of careful invisibility among his classmates, and he spends most of his time making mediocre films with his only friend, Earl.

Greg's mother insists he rekindle a friendship with Rachel, who is struggling with her illness. This new connection brings both awkwardness and genuine human moments. As Rachel decides to stop treatment, Greg and Earl set out to make a film for her, which leads to unexpected personal growth and emotional revelations for the boys. The story navigates the complex terrain of adolescence, illness, and self-discovery with a blend of wit and sensitivity.