When California resident Susan Murphy (Reese Witherspoon) mysteriously grows to 49 ft 11 in, she is labelled a monster and captured by the military. She is remanded to an institution that houses other monsters: Dr. Cockroach, Ph.D., an insect-headed mad scientist (Hugh Laurie), the Missing Link, a thousands-of-years-old fish-man (Will Arnett), B.O.B., a gelatin-like, jolly, indestructible monster (Seth Rogen) and Insectosaurus, a fuzzy bug (Jimmy Kimmel) that stands at 350 feet tall, making even Susan look tiny by comparison. When a UFO lands and an alien overlord named Gallaxhar (Rainn Wilson) demands that Earth be given to them, General W.R. Monger (Kiefer Sutherland) suggests to the President (Stephen Colbert) that the monsters can provide the firepower to defeat the aliens.