Cristina, Izzie and Meredith take care of Shane, a man who appears to be crazy and claims that he is pregnant. Shane's case induces a spreading fascination among the staff. George relates to a patient's husband.

The staff attends to an intern from another hospital who has short-term memory loss. This intern, named Marshall, also has caused a car accident that involved a married couple, their unborn baby and the woman's parents who the staff are also treating. The pregnant woman is named Melanie and she will die but her baby may survive. One of the female interns meets up with a woman from her past who is planning on having a family of her own. Cristina is in a good mood although Alex, Izzie, George, and Meredith are having problems but in the meantime Burke hasn't forgiven Cristina for her late night faux pas. Meredith and Izzie are making fun of Callie's household habits and George and Callie are having a fight because of George's roommates. Addison is continuing to own Alex and he's upset about it. Denny has an outburst at Izzie and Derek has an outburst at Meredith.

The race for the Chief's position is on, and the attending physicians, Derek, Burke, Addison and Mark, compete for Richard's affections by trying to help out everywhere possible. The Denny Duquette Memorial Clinic is open for business, but only one single patient shows up. Izzie is disappointed in what she invested Denny's legacy in, and tries to steal patients from the emergency room. Callie and George get back from Las Vegas, announcing their marriage, much to everyone's disbelief. Izzie is not supportive of their marriage and tries to get George to realize the mistake he has made. Meanwhile, Meredith's Alzheimer's-stricken mother, Ellis Grey, experiences a change in her medical condition by becoming lucid for the day. She is disappointed in the mediocrity her daughter has fallen into and begins to despise Derek, blaming him for what happened to the Meredith that used to be "a force of nature". Ellis has to have heart surgery and, despite her wishes, Meredith schedules her upcoming surgery. Richard talks to Ellis and realizes that she is still in love with him, but loses her memory after their talk ends, before Meredith has the chance to tell her how she really feels.

A face familiar to one of the year-twos shows up and dredges up issues that were never really dealt with. A teen soccer player needs counseling because of his father and surgery for an injury he sustained while playing the game. Another patient's, named Courtney, finds out that her cancer is back.