When the Littles adopt Stuart, the mouse, George is initially unwelcoming to his new brother, and the family cat, Snowbell, is even less enthusiastic. Stuart resolves to face these difficulties with as much pluck and courage as he can muster.

Stuart, an adorable white mouse, still lives happily with his adoptive family, the Littles, on the east side of Manhattan's Central Park. More crazy mouse adventures are in store as Stuart, his human brother, George, and their mischievous cat, Snowbell, set out to rescue a friend.

With school out for the summer, The Littles are vacationing in a cabin by the lake, and Stuart is so excited he could burst! But when Snowbell the cat is captured by a mean-spirited creature known simply as the Beast, it's up to Stuart and a skunk named Reeko to rescue him and a few other friends.