Mother

Since she had received no alimony from ex-husband Paul Simon, Albert Brooks asked good friend (and daughter of the movie's star Debbie Reynolds), Carrie Fisher, if she would ask her ex to give Brooks the right to use an adapted version of his famous song "Mrs. Robinson", which had originally been used in the film The Graduate (1967). Both Simon and his equally famous partner Art Garfunkel had previously refused to allow anyone to use their iconic song. For instance, in the early eighties, the duo were offered a lot of money to rework the song for a "Mr. Coffee" commercial. They refused that and all other offers. However, because of his relationship with Fisher, Simon agreed, and the song was rewritten using the name "Mrs. Henderson" instead.

Director/writer/actor Albert Brooks asked Nancy Reagan (who used to act under the name Nancy Davis) to play the part of his mother. Nancy really wanted to come out of acting retirement to play the role, but declined because she couldn't bear to be away from husband and former president Ronald Reagan, suffering from Alzheimer's disease. Also on Brooks' list of former actresses to play his mother was Doris Day, but she showed no interest in coming out of acting retirement. Brooks is an old friend of actress/writer Carrie Fisher, and he knew her famous mother (Debbie Reynolds) through her. (Debbie used to try to pair Albert and Carrie off for marriage.) Brooks was looking for a big-name actress from the past and called Fisher to see if she thought her mother would accept the role. Fisher said yes, as did Reynolds.

Though they play mother and son in the film, in actuality Debbie Reynolds was only 15 years older than Albert Brooks.

Brooks also met with Esther Williams to discuss the role of Mrs. Henderson.

Kathryn Grayson was supposedly offered the title role but turned it down saying she couldn't possibly because the mother was "brain dead".