The producers pitched the series to ABC as a relatively straightforward buddy comedy in the spirit of Billy Wilder's comedy films. When they used the film Some Like It Hot (1959) as an example, the network agreed to the series, but only if the main characters were disguised as women. Although the producers had to change the series quickly, they were able to produce it with little network creative interference.
In an interview in TV Guide, Donna Dixon explained how she landed the role of Sonny, her acting debut. She knew that as an unknown she would be competing against a lot of women. To stand out, she wore a bright red tracksuit to the audition.
Tom Hanks first meet his future wife, Rita Wilson when she made a guest appearance in this series in "All You Need Is Love" in 1981, but both were in other relationships at the time. They began dating a few years later when they met again on the set of Volunteers (1985).
Cast member Thelma Hopkins was in the music group Tony Orlando and Dawn as a vocalist. She showcases her singing talents in many Bosom Buddies episodes. In the episode "One For You, One For Me", in which Kip goes to jail, Thelma Hopkins makes a reference to tying a yellow ribbon around the old oak tree in front of their building. "Tie a Yellow Ribbon" was Tony Orlando amd Dawn's biggest hit single.