The team has a hard time trying to understand Michael who has become a team member since Grissom’s teaching hiatus. They investigate the murder of an unidentified girl who may have been killed by a serial killer who has been killing since the early 1970’s.
Cristina and Burke continue to play Uncle until one of them gives in. Derek and Meredith are fighting over the reason for their sleepless nights. Meredith tries to talk to her father about his side of the story. There's tension between Alex and Addison. There is even more tension between Addison and Mark. Addison confides in Callie. Bailey wishes she didn't have to keep a secret from one of the interns. Callie rushes to be with George after she learns that his dad needs an emergency procedure. Izzie may have found 'some good to do' with her inheritance.
Dave promotes the new, improved Late Show web site; "El Nino" (Gerard) drops by to take a bow; Vera Farmiga promotes "Breaking and Entering"; Mat Kearney performs "Nothing Left to Lose."
Sam and Dean investigate an Connecticut inn run by a single mother where mysterious deaths are taking place. They find evidence of Hoodoo, and try to figure out who is causing the chaos.
The big day is here, so Stephen is crazy with anticipation that Bill O'Reilly will be on the show, stating that his only goal with this show was to see this day, which makes him reveal a "Mission Accomplished" banner and open the last door on his "Bill O'Reilly advent calendar" (in which he finds Geraldo's mustache). He then turns back to US politics talking about Bush's plans to rise the troop levels in Iraq. He then talks about fights between celebrities on his segment "We the MEdiator", rethinking his last week's judgements.
Oscar returns from his vacation and ponders his future with the company, while Andy takes advantage of the current state of the office to make a move towards becoming Michael's number two.