Gone Daddy Gone
performed by Gnarls Barkley

The episode begins with Meredith running out of Seattle Grace, choosing neither Finn nor Derek. The interns help Izzie cope with the loss of her fiance, Denny. Meredith begins to deal with the aftermath of the prom, concerning the Finn/Derek love triangle. Addison, devastated, discovers a pair of black panties in Derek's tuxedo jacket and knows the owner is Meredith. She washes them and then posts them beneath a "Lost and Found" sign in the hospital hallway. Addison has a sexual relationship with Derek's best friend, Mark Sloan. Derek went to end his and Addison's relationship. He went to the hotel room Addison was staying at, telling her that their marriage is over. From the bathroom emerges a naked Mark Sloan with a towel. Derek is shocked and leaves. Derek makes no secret of his desire to end his marriage and be with Meredith. In the end, both men tell her they will wait for a decision. The Chief is confronted by his wife Adele and is given a very difficult decision (retire or divorce) that he must soon make. George and Derek get quarantined when there is an outburst of the plague at Seattle Grace. Derek gives George relationship advice concerning Callie. After speaking with the Chief, Cristina realizes maybe she has taken her relationship with Burke for granted. Flashbacks happen, including when Derek meets Meredith, when Addison is caught cheating on Derek, the mixer the night before the interns begin their first shifts, and when the Chief ends his affair with Ellis Grey. Meredith has to choose between Derek or Finn.

Vince and the entourage head to Las Vegas for a vacation and for Vince to make a special promotional appearance for $100,000. Seth Green repeatedly harasses Eric about Sloan. Drama misleads a masseur after showering him with compliments.