"The Simpsons" was created by , Matt Groening, who is a huge Zappa fan. Zappa was to have supplied a voice for The Simpsons, as he had done for Ren & Stimpy, but became too ill before he could record his part.
In the episode "The Girl Who Slept Too Little" (2005) The Simpsons walk into a convention. The banner welcomes visitors with the words: "Welcome to the Fathers of Invention", with the words "And Mothers" scribbled above it.
In the episode "A Midsummer's Nice Dream" (2011) Homer takes Bart and Lisa to his the attic to let them listen to his old Cheech and Chong albums. In a brief scene a copy of the rock magazine "Crawdaddy" can be seen with Zappa's face on the cover.