This episode was originally aired on February 12 2006, the day of Christina Ricci's 26th birthday who is a guest star in the episode.
Cristina and Izzie helping Meredith into the shower towards the end of this episode mimics George's dream at the beginning of its prequel.
Every episode of the show is named after a famous song. "It's the End of the World as We Know It" is a song by R.E.M..
Izzie says she's the kind of girl who laughs at a funeral. This is very similar to a line in the song One Week by Barenaked Ladies.