Dr. Derek Shepherd (Patrick Dempsey) is the head of neurosurgery at Seattle Grace Mercy West Hospital. Derek came to Seattle after he caught his wife in bed with his best friend. His good looks and personality earned him the nickname "McDreamy." Derek is the youngest of five siblings and all of his siblings are female. He is an extremely talented neurosurgeon and on more than one occasion Dr. Richard Webber (James Pickens, Jr.) has referred to him as the man with "$2 million dollar a year hands." He meets Meredith Grey (Ellen Pompeo) the night before he starts work at Seattle Grace and has a one-night stand with her. When he realizes that she is an intern at Seattle Grace he pursues her until she agrees to start dating him. However their happiness is short-lived when his wife, Dr. Addison Montgomery-Shephard (Kate Walsh) shows up in Seattle and informs Meredith that Derek is married.
Derek decides to give his marriage with Addison a second chance and breaks up with Meredith. He and Addison enter therapy but their reconciliation is complicated by Derek's continued friendship with Meredith and the arrival of Dr. Mark Sloane (Eric Dane), the man that Addison cheated with and Derek's best friend. Throughout the season the unresolved romantic tension between Derek and Meredith continues to build and they eventually have sex in an exam room during the hospital prom.
Later Derek asks Addison for a divorce and reunites with Meredith. Their relationship is strained when Meredith almost drowns in the Puget Sound. Derek tells Meredith that he can't breathe for her. In the season finale Meredith breaks up with Derek.
Although Derek and Meredith have broken up, they continue to meet in the on-call room for break-up sex. Derek tells Meredith that he wants someone he can have a real relationship with and starts dating a scrub nurse, Rose (Lauren Stamile). Later in the season Derek helps Meredith with a clinical trial for shrinking malignant tumors. Although they lose a number of patients, their last patient in the trial is a success. Meredith tells Derek that she's ready to be with him and they reunite for good.
Derek finally proposes to Meredith. They plan an elaborate wedding but eventually decide to give their wedding to Alex Karev (Justin Chambers) and Izzie Stevens (Katherine Heigl) because Izzie is suffering from cancer. Instead Derek and Meredith write their vows to each other on a post-it note which is referred to the other members of the hospital as "the post-it note wedding." In Season 6 he is approached by the board of the hospital and asked to take over as chief of surgery. Although he declines the position he questions some of the decisions that Dr. Webber is making. When he learns that Richard is drinking again, he convinces him to go to rehab and takes over as interim chief of surgery.
"This is a good day to save lives. Let's have some fun."
"I'm just a guy in a bar."
"You were like coming up for fresh air.