Brian is still atheist despite meeting Jesus in "I Dream of Jesus" and getting proof that he can perform miracles. In "If I'm Dyin', I'm Lyin'", Brian has seen plagues that were inflicted on the family.
Adam West plays both Mayor Adam West, in cartoon form, and himself in a live action piece with Rob Lowe.
In "Love, Blactually", Stewie mispronounces the word 'ruined' as 'rueeened', but when he is berating the cast for ruining his day, he pronounces the word 'ruined' normally.
Patrick Stewart is annoyed when Stewie pronounces "Wil Wheaton," "Whil Wheaton." However, in Star Trek: The Next Generation, Patrick Stewart's character commonly pronounces words "hw" instead of "wh".
While at the McDonald's drive-thru, Michael Dorn asks for a McDLT, which was discontinued in 1990. He also asks whether McDonald's has beer. Beer is sold at McDonald's only in some European countries.
In the bowling alley, Wil Wheaton is operating a crane machine in the background. He is pulling up Rupert.
Stewie takes a picture of Meg with his cell phone and sends it to Calvin from the Calvin and Hobbes comics.
One of the books the dogmatic Christians throw into the fire is Charles Darwin's Of the Origin of Species, a book which has suffered a lot of controversy over the fact that it introduced the theory of Evolution.
Due to a legal matter, this episode was temporarily pulled from all online distribution including hulu and iTunes.
In a scene removed after the initial broadcast, Peter asks William Shatner at a convention: "Yes, I have a question for Captain Kirk...in that episode where you drown your wife; Why are you so fat?" Although it's a reference to the episode The Paradise Syndrome, William Shatner's wife Nerine Kidd drowned in a pool accident in 1999.