The premise of the show, as established already in the first episode, involves a recently widowed San Fransisco sportscaster (later television talk show host), Danny Tanner, who is left to raise his three young daughters D.J., Stephanie, and baby Michelle following the death of his wife, Pam, in a car accident involving a drunk driver. He recruits his best friend from college, Joey Gladstone, and his late wife's younger brother, Jesse, to help him take care of his girls. It's worth mentioning that many of the show's exploits surrounded the idea of three "swinging" bachelors trying to rein in the precocious antics of three little girls, who frequently got the best of them. Joey makes a living primarily as a stand-up comedian and Jesse as a struggling musician who originally pays the bills working for his father's exterminating company. Jesse eventually quits his exterminating job, much to his fathers disapproval, and starts up in advertising alongside Joey. While trying the the break within the music business, Jesse has a number of jobs during the shows running but also gets his big break. At the beginning of the second season, Danny becomes the co-host of the morning talk show "Wake Up, San Francisco" alongside Rebecca Donaldson. Jesse and Becky begins dating during the shows second season, and has many a humorous antics involving their relationship, mostly about how different they are. But despite their differences, they get married during the shows fourth season and during the fifth season they get twin sons, Nicky and Alex. The girls grow up considerably as the series goes on, and often argue and clash as sisters often do. The expanded family all live together in the same "full" house. To quote the theme song, "Whatever happened to predictability?"

The show survived extremely critical reviews during its first season, based on the series core as a form of family entertainment. Although it would maintain its very family friendly material for the entire series, criticisms eventually became much less intense.