Callie Torres (Sara Ramirez)
Overcome with piles of paperwork and her increased dependency on Dr. Bailey's help, Callie must leave her post as the new Chief Resident and return to her old position as an orthopedic surgeon. As her career shakes up, so does her love life. A "McSteamy" romance is rekindled, and feelings for the new head of cardiothoracic surgery surprises all.

Derek Shepherd (Patrick Dempsey)
Questioning Meredith’s commitment to their love, Derek and Meredith split up. But, as he partners with Meredith on a new clinical trial, he must reconcile his feelings for her with his new romance with Nurse Rose.

Erica Hahn (Brooke Smith)
The new Head of Cardiothoracic surgery, Erica joins Seattle Grace and tries to maintain power over her staff, particularly Cristina. While rebuffing the advances of the flirtatious Dr. Mark Sloan, she is confronted by another, unexpected advance – from Callie Torres.

Lexie Grey (Chyler Leigh)
Stunning Meredith, Lexie confesses that she is Meredith’s half-sister. As Derek also mentions to Meredith that Lexie is “the girl at the bar,” Lexie must fight an uphill battle to establish a relationship with Meredith. Instead of connecting with the other interns, Lexie finds a new friendship with George – or, maybe more.

Mark Sloan (Eric Dane)
Along with a renewed friendship with Derek, Sloan finds himself in the midst of an infatuation with Dr. Erica Hahn. A comfort to Callie, Sloan helps her through her divorce from George, leading to a casual relationship that may eventually include more than just two parties.

Richard Webber (James Pickens Jr.)
After separating from his wife, Richard realizes how special his relationship was. He comes to learn how little he invested in his marriage, given all that was sacrificed for him. Richard experiences heartbreak, followed by nights camping with the boys trying to heal. Being a bachelor is not as much fun as he remembered. A loss brings Richard and his wife back together, as hardship helps them re-build their marriage.