At Monsters, Inc. it's the job of a wide variety of monsters to enter children's bedroom closets at night, scare them, and then collect their screams that provide the power for Monstropolis. According to the crab-like CEO, Henry J. Waternoose (voice of JAMES COBURN), however, human kids have become harder to frighten, and thus the monsters are facing an energy shortage.
Thus, he wants James "Sulley" Sullivan (voice of JOHN GOODMAN), the top "scarer" at Monsters, Inc. to teach the new recruits how to spook children. A furry, blue-haired monster, Sully is good at his job - thanks in part to the prep work done by his assistant and roommate, Mike Wazowski (voice of BILLY CRYSTAL), a squat, one-eyed green monster - but now faces competition from Randall Boggs (voice of STEVE BUSCEMI), a scheming, eight-legged creature who can turn invisible.
As their competition intensifies, they all know the guiding principle that children are toxic, contact with them is very dangerous and that they're never, ever, to allow any of the children to cross through the closet door and back into the Monster, Inc. factory. Yet, that's exactly what happens when the cranky office manager, Roz (voice of BOB PETERSON), demands that Mike turn in his late reports. Since he has a date with the Medusa like Celia (voice of JENNIFER TILLY), Sulley decides to do the work for him.
When he goes to retrieve the paperwork, however, he notices one closet door that's been left on the factory floor. Going to investigate, he inadvertently allows a young girl, Boo (voice of MARY GIBBS), to cross over into his world. Scared of the girl who sees him as just a big furry plaything that she calls "Kitty," Sulley panics and tries to figure out what to do.
Getting Mike involved with his new problem, the two try to hide the girl and get her back into her world before anyone sees her with them, all while uncovering a diabolical plot that Randall has hatched.