Empty Nest originated from a 1987 Golden Girls episode called "Empty Nests," intended as a backdoor pilot featuring George and Renee Corliss, a middle-aged couple with empty nest syndrome, but that version never went to series.

The original pilot concept was partly conceived as a star vehicle for David Leisure, who had become a national celebrity playing car salesman Joe Isuzu, though his character was originally named Oliver rather than Charley.

Rita Moreno, who played Renee Corliss in the unaired pilot version, later called it a "very, very bad show," explaining that creator Susan Harris was too sick during shooting week to fix the script, forcing other writers to constantly rewrite her character until she could barely remember her lines after about 15 takes in front of a live audience.

Although the pilot's premise was scrapped and recast entirely, the set of the Corlisses' house was reused exactly as it was and became the Weston family residence in Empty Nest.

Empty Nest, The Golden Girls, and Nurses all aired on NBC on the same night, set in the same city with characters who knew each other from the start, one of the few times in American TV history three shows from the same producer crossed over this way; Susan Harris even wrote storylines that carried through all three series as fictional crossovers.

Richard Mulligan and Dinah Manoff, who played father and daughter Harry and Carol Weston, had previously played father-in-law and daughter-in-law on the show Soap, created by the same production team; Jay Johnson, who played Mulligan's son on Soap, also made a guest appearance on Empty Nest.

The theme song "Life Goes On," written by John Bettis and George Tipton and performed by Billy Vera, was presented in a slower, melancholy-yet-comical arrangement for the first three seasons before switching to a higher, more upbeat version with female backup singers for the final four seasons.

Richard Mulligan won both an Emmy Award and a Golden Globe Award for Best Lead Actor in a Comedy Series in 1989 for his role as Dr. Harry Weston.