Larry Daley is a divorced father who can't seem to keep a job for more than a week. As a last resort, Larry applies for a job as a night shift security guard at the American Museum of Natural History. However, a seemingly easy job turns out to be an adventure when he finds that an ancient curse causes the "inhabitants" of the museum to come to life at night.

When the Museum of Natural History is closed for renovations, the museum pieces are moved into federal storage at the famous Smithsonian Institution. It houses the world's largest museum complex with more than 136 million items in its collections. These range from the plane Amelia Earhart flew on her non-stop solo flight across the Atlantic and Al Capone's rap sheet and mug shot to Dorothy's ruby slippers. From Fonzie's leather jacket to Archie Bunker's...