First appearance of Cletus' daughter, Mary (Zooey Deschannel).
Mr Plopper from The Simpsons Movie appears.
The "anguished animal" CD Lisa and Bart listen to is by Tress McNeil who voices some Simpsons characters such as Agnes Skinner and Brandine Spuckler.
The title "Apocalypse Cow" is a play on words for the similarly named movie, "Apocalypse Now"
The laughter house/slaughterhouse reference was similar to the "(s)laughter is the best medicine" reference made in The Dark Knight (2008), released 2 months after this episode aired.