This episode was broadcasted right after the Super Bowl.

This episode did not feature the opening credits sequence.

In conjunction with "(As We Know It)", this episode was nominated for the 2006 Emmy Award for Outstanding Writing For A Drama Series.

This episode is presented in an 'uncut and extended' version on the second season DVD.

This episode was voted #32 on the Futon Critic's 50 Best Episodes of 2006 article.

Meredith: Okay. The man I love has a wife, and then he chooses her over me. And that wife takes my dog. Okay, she didn't take the dog, I gave it to her, but I didn't mean to give it to her, I meant to give it to him. But that does not change the fact that she's got my McDreamy. And my McDog. She's got my McLife. And what have I got?

Meredith: I have a feeling.
Derek: I get those.
Meredith: Yeah?
Derek: Yeah.
Meredith: And?
Derek: If you wait long enough, it passes.
Meredith: Promise?
Derek: I promise.
(Meredith walks away, and Addison walks in)
Addison: Hey ... what'ya doing?
Derek: Waiting for it to pass ...

Izzie: We're watchers. We have to become more proactive, George. We have to become doers.
George: Fight for what we want.
Izzie: We have to do.
George: Yeah.
(George looks confused at Izzie as she's standing up)
George: Oh, you mean, starting right now. Okay.

Dylan Young: You close him up, you do whatever you have to do. The Chief of Surgery has authorized me to tell you that you can not stay here.
Derek: The Chief of Surgery doesn't scare me. Dr. Bailey scares me. I'm not going to be the one to let her husband die. (..) Now get out of my OR.

Episode Title: It's the End of the World (As We Know It)

"It's the End of the World (As We Know It)" is a song by R.E.M.