Producers wanted "someone like Betty White" to play Sue Ann Nivens. Eventually, someone asked, "Why not cast Betty White?"
According to a 2013 interview with Valerie Harper and Cloris Leachman on the TV show "The Doctors," this was the first (scripted) show in TV history ever to use the word "gay" to refer to homosexuality (in the season three episode "My Brother's Keeper") when Rhoda tells Phyllis that Phyllis's brother is gay.
In the episode where Mary had her tonsils removed, originally she was going to have a tattoo removed. Ms Moore in real life refused saying she was a "good catholic girl" and she "couldn't play that," so they changed it to a tonsillectomy.
Producers almost didn't hire Valerie Harper because while her performance was spot on, they felt she was too pretty to play Mary's frumpy best friend. They later decided to cast her anyway but would dress her in ungainly and frumpy clothing.
Gavin MacLeod and Cloris Leachman were not close in real life, much like their characters. They had worked together before and had a very bad experience, and Cloris was actually uncomfortable with Gavin for the first couple seasons, and didn't want to be near him on the set. Eventually they grew to be friends, though.