The title of this episode refers to the saying "Life is a bitch."
60 Minutes After Dark, a show Peter and Lois watch, is a combination of the news show 60 Minutes and the raunchy variety show Playboy After Dark.
Peter passes a black cat, a raven, and a Black man, the former two of which are traditionally seen as hearbingers of bad luck, and the third a play on the word "black."
Peter mistakes the lump in his breast (a fatty corpuscle) for comedian Fatty Arbuckle.
When Peter asks Death "Who are you?" he answers "I'm Calista Flockhart," referring to the actress' thin and bony frame.
Stewie says that his last helping of white meat was "dryer than Oscar Wilde," referring to the Irish writer's sense of humor.
When Death eats an entire turkey leg in one bite, he attributes the ability to "some films" he appeared in. This is a reference to the act of deep throating in pornographic films.
Death's remark to Peter, "Hey, I caught Flo-Jo," is a reference to the untimely death of runner Florence Griffith Joyner.
When Death decides to stay with the Griffins, Peter objects saying, "How are we supposed to explain you to Mr. Roper?" referencing the original landlord, played by Norman Fell, from the sitcom Three's Company.
The pilot of the plane points out the San Fernando Valley beneath the plane where his brother "makes a very nice living directing porn." San Fernando Valley is the center of the US pornography industry.
Actress Karen Black successfully lands the plane, as her character did in the film Airport 1975. Newscaster Tom Tucker calls it "an obscure reference." He also mentions her other films Five Easy Pieces and Nashville.
The varied passengers on the plane, nuns, Girl Scouts, etc, are reminiscent of the film Airplane!, which spoofs the disaster movie genre.
Stewie uses a tricycle to push Lois down a flight of stairs, a reference to the 1976 thriller, The Omen.