The main character is "Susan", a (painfully) normal young California woman (voiced with trademark cluelessness by Reese Witherspoon). After an opening sequence too thick in old movie references to count, she is struck by an eerily glowing meteorite just before her wedding, which comes to a halt when she begins to transform into a "fifty foot woman".
Dazed and confused by her metamorphosis, she is subdued and captured by government troops, and wakes up in a Guantanamo-like holding facility. While topical, this sequence is a bit jarring and brutal as initially she is given no explanation as to where she is or why she is being held. Then, her captor, General W.R. Monger (Kiefer Sutherland) explains to her that since she is now a monster, she no longer has rights and can only look forward to a lifetime of incommunicado imprisonment.
However, she isn't quite alone in the facility. It also holds genuine 1950's era creatures: the bug-human science error Dr. Cockroach (Hugh Laurie), The Missing Link (Will Arnett), B.O.B. (Seth Rogen), and Insectasaurus. Think; "The Fly" (Dr. C even has a Vincent Price mustache), "The Creature from the Black Lagoon", "The Blob," and "Mothra," and you'll have the cast. Things change when a gigantic alien robot commanded by Gallaxhar (voice, Rainn Wilson) lands. Gallaxhar is a macrocephalic tentacled evil alien overlord who wouldn't have been out of place in the "Mars Attacks" bubblegum cards, as well as sharing a resemblance to "The Mekton" from the British "Dan Dare" comics of the period.
General Monger sees this as his big chance to become something other than a jailer, and, after conventional attacks on the robot fail, convinces the egotistically idiotic president (Stephen Colbert) to let him send in the monsters as shock troops.
This is initially a pretty traumatic experience for Susan, since a) she has no combat training or skills whatsoever, and b) as large as she is, the robot is twenty times larger and heavily armored to boot. Rescuing the endangered populace is a powerful motivation, though, and in the process of defeating the robot, Susan discovers that the meteoroid energy has made her super-strong, even for her size.
This victory wins the monsters their uneasy freedom, which results in a lot of problematic interaction with Susan's family and her fiancé, until Gallaxhar arrives in person with his even more huge mothership--.
While pure fun and a great homage to Cold War era SF films, the movie has lots of good, if not terribly original "girl power" message as well. Animation and design are up to Pixar standards, especially the scenes aboard the alien spacecraft. Witherspoon, Rogen, and others in the monster cast are doing well-established character tropes competently, while Sutherland and Colbert chew the war-room walls ala "Dr. Strangelove".
Good fun, best if you get the jokes. OK for kids old enough to not get freaked out by the monster-movie violence.