Fred Gwynne was originally cast to play Henry but backed out when, in an audition for the role of Henry P. Warnimont, he was identified as Herman Munster, which was his role on The Munsters (1964).
Cherie Johnson is the niece of the show's creator and producer, David W. Duclon, who named the character for her. Nevertheless, she auditioned for the role like everyone else and was picked by the network to play the part.
Then-NBC programming chief Brandon Tartikoff helped develop the show, naming Punky Brewster after a girl he had a crush on in school. The real Punky Brewster was married to a lawyer in Connecticut and received a royalty check to use her name. She made a cameo appearance in one episode as Punky's teacher.
Melissa Joan Hart originally auditioned for the part of Punky Brewster. Coincidentally, Soleil Moon Frye, who got the part, later co-starred with her on Sabrina the Teenage Witch (1996).
The program-producing unit of NBC produced the first two seasons. After its cancellation, the show sold to Columbia Pictures Television for $60 million. However, Columbia made the latter two seasons for syndication (though there is a one-year interval between them) without NBC's involvement.