After Danny Tanner's wife Pam is killed in a collision by a drunk driver, he recruits his rock musician brother-in-law Jesse and quirky comedian best friend Joey to help him raise his three daughters: D.J., Stephanie, and Michelle, in his San Francisco home. Over time, the three men as well as the children bond and become closer to one another.

Initially, Jesse is uncertain if his life is going in the right direction after making the life-altering decision to help raise the girls. In season two, Danny becomes host of a local television morning show. His co-host, Rebecca "Becky" Donaldson, starts dating Jesse, and eventually becomes his wife and joins the household. The family finds a dog and keeps one of her puppies, Comet, as a pet. Finally, Jesse and Becky have twin sons, Nicky and Alex, who become additions to the family. Two notable additional characters are Kimmy Gibbler, D.J.'s best friend and the Tanner family's annoying neighbor, and Steve Hale, D.J.'s boyfriend.