A run-in with her old flame Sean and an accident in her new car lead Elliot to the realization that nothing good has happened to her in the three years that she has been at Sacred Heart. This realization drives her to take drastic measures, including a complete makeover, both inside and out, in an attempt to change her luck. Meanwhile, J.D. gets stuck with a patient, whose diagnosis he can't quite pin down, and when Dr. Cox denies him any assistance, he looks to Carla and Turk to help him out. While Dr. Cox is busy not helping J.D., he takes the time to make amends with Dr. Kelso.

J.D. is feeling left out of his friendship with Turk and gets hurt when Turk is scared of opening up to him. Meanwhile, Carla is driven crazy over an unidentified urine sample, and Elliot tries to balance Sean and her career, so that one doesn't end up getting in the way of the other.

Finding difficulties training his interns, J.D. asks to Elliot for some help. She tells J.D. about Sean, who gave Elliot great tips based on his dolphin training that fit perfectly for her interns. Dr. Cox finds the ideal pediatrician for his son: Dr. Norris, who acts and looks just like him. However, Dr. Cox is quick to find a problem with him once Jack develops a cough that scares both him and Jordan.

Sean is a bit surprised and disturbed to learn about Elliot and J.D.'s history together, but it turns out his anger is really a cover up for his upcoming six month long trip and he doesn't want Elliot to explode. Dr. Cox. is forced to swallow his pride and actually ask for help when he decides to throw his hat in the ring for the Residency Director position at the hospital. Carla picks up an extra shift as a surgical nurse, which allows her to spend the day working alongside with Turk, to his great annoyance.

Dan decides to stay with J.D. for a while after their mom's new fiancé kicks him out, but after spending some quality time with him at the hospital, Dan isn't sure if he likes the cynical person his little brother has become. Elliot tries to deal with her own problems of a long distance relationship and decides to try moonlighting as a pet examiner with Carla to save up money.

A chance meeting in the elevator sparks a new friendship between J.D. and the mysterious Danni whose ongoing dialogue about her ex forces J.D. to talk about his feelings for Elliot. Carla's brother Marco comes to visit, but he still hasn't forgiven Turk for mistaking him for a valet at their mother's funeral. Unfortunately, Turk can't even apologize because Marco can't speak anything but Spanish. At the hospital, Dr. Cox relishes his new job promotion but is surprised when J.D. doesn't follow his lead in contradicting Dr. Kelso's orders.

As J.D.'s relationship with Danni progresses, he and Dr. Cox are forced to spend more time together outside of the hospital, to Perry's great chagrin. Meanwhile, as they each deal with problems in their own relationships, Carla and Elliot work to find their own balance between their personal and professional relationships. Dr. Kelso accidentally punctures his eardrums giving the hospital staff an opportunity to tell him how they truly feel about him.

Turk is happy that he finally makes it through a solo surgery without the assistance of an attending surgeon. Dr. Cox dreads the fact that he is getting older. J.D. also makes a discovery as he finds out that many of the hospital staff don't know the Janitor as he does.

Elliot is feeling uncomfortable using clinical terms for her patient's private parts – a result of a repressed childhood and an accidental orgasm she inflicted on a patient during a pelvic exam - so Carla tries to teach her how to say "vagina" and "penis" without blushing. Meanwhile, Dr. Cox crashes at J.D. and Turk's after taking bad advice from J.D. Carla suggests no more sex until the wedding and Turk only comes to terms with it after learning the real meaning of romance from a patient with prostate cancer. Ultimately Carla backs down on her own idea when she has a stressful day at work finally letting people make fun of her.

Carla and Elliot try to help a patient, Maggie, lose her virginity as she prepares to die. Walking in on her sister and Dr. Cox prompts Danni to move in with J.D. Dr. Cox attempts to convince Turk to do a kidney transplant for a patient he has "moved up" the list. But a personal grudge seems to stand in the way and may decide whether the patient lives or dies.

J.D. tries to break-up with Danni, but she beats him to it when she realizes that she will always be second place to Elliot in his heart. Dr. Cox suddenly becomes a nice guy and Elliot changes back to her old self after Dr. Kelso criticizes her new look.

J.D. believes he may have finally found a mentor in Dr. Kevin Casey, a surgeon with obsessive-compulsive disorder, and it turns out that Dr. Cox has always been jealous of the guy. Meanwhile, the Janitor and his new assistant help Kelso out with a garbage problem.

Elliot finds herself perplexed over a simple procedure that leaves her questioning her career path. She goes to seek Dr. Kevin Casey's advice but becomes frustrated when she learns that the epiphany toilet, which the Janitor secretly installed on the roof, is getting more attention than she is. Meanwhile, Turk asks J.D. to be his best man at his wedding, which sends J.D. into sheer bliss momentarily until he hears a phone message that makes him question his friendship with Turk.

Jordan's brother and sister return, but Dr. Cox learns that his brother-in-law Ben hasn't visited a doctor about his cancer in the two years he has been gone traveling the world.

Jordan's friends Allison and Maddie come to town to provide moral support for Jordan after her brother's death – however, their constant presence does not provide any relief to Dr. Cox. Meanwhile, Turk tries to impress the new female surgeon, Dr. Miller, but his first encounter serves only to leave him baffled by the opposite sex yet again. Attempting to reinforce the policy on sexual harassment at Sacred Heart, Carla is forced to teach a course where Dr. Kelso is the number-one student.

An ever present butterfly prompts the question on what could have happened different as Turk looks for his lucky do-rag for surgery, and Elliot tries to find a lost stuffed animal for a child needing a bone marrow transplant.

J.D. must keep a secret when Carla's "what-if" guy asks her out on a date. Meanwhile, on the other side of the argument, Carla hounds Turk for checking out other women. Elliot is also on the spot as Dr. Cox and Dr. Kelso both advise her not to give her patient drugs as they suspect he is an addict faking pain.

Turk has to confront a young patient of his, when he accidentally cuts a nerve and the boy (who happens to be a concert pianist) loses use of one of his hands. Meanwhile, one of Elliot's patients unintentionally teaches her a lesson about her relationship with J.D.

J.D. hooks up with Danni again, after Sean returns, but he can't forget about his passionate night with Elliot. Meanwhile, Dr. Cox realizes, that he might actually have a crush on the one doctor he loathes.

Elliot asks Sean to move in with her, which only adds to J.D.'s problems. Turk is unsure why Dr. Miller's attitude towards him has changed, until he finds out that Carla un-invited her from their wedding. Dr. Kelso outrages Dr. Cox when he announces that Sacred Heart will begin doing full body scans, starting with an ever present hypochondriac patient, who wants any freebies he can get.

J.D. is unsure what to do, when he realizes he made a mistake telling Elliot he loved her. The Janitor squares off against Dr. Cox after he loses the election of the janitors to Randall. Carla's brother Marc constantly puts Turk in a tough situation, when Turk forgets to write his wedding vows.

The big day for Turk and Carla has finally arrived, but a patient holds up Turk. With Elliot still angry at him, J.D. attempts to reconcile her with Sean as a way to make everything right again in their friendship.