As Sean reluctantly celebrates his 40th birthday, Christian urges him to take advantage of some of the youth-preserving treatments available at the clinic. But Sean vows to grow old naturally. Much more upsetting, however, are the occasional muscle spasms that Sean experiences during delicate surgery, prompting him to visit a neurologist. Although he is not the father, Christian agrees to help raise the baby of his former sexual partner, Gina Russo causing him to reevaluate his priorities. And both men must cope with the ramifications of a surprise visit from Julia's narcissistic mother, Erica Noughton, who demands plastic surgery for a younger appearance.
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After Sean nicks a patient's major neck artery during a routine cyst lancing, Sean stops performing surgeries. He becomes even more depressed and anxious when Christian, whose nose has been broken by a woman during sex, asks another plastic surgeon to reset it. Christian is deeply insulted when the attractive female surgeon not only rebuffs his sexual advances but also advises him to get some cosmetic work done on the rest of his aging body. And after botching an attempt to operate on himself in a mirror, Christian bolsters Sean's confidence by confessing that he only trusts Sean to do the job correctly.
Christian and Sean agree to rehabilitate a stalwart, optimistic Somali woman, Manya Mabika, who was genitally mutilated as a girl in her home country. After they surgically rebuild her clitoris, Manya asks the perfectly willing Christian to help her have an orgasm, but even he cannot succeed, causing the doctors to worry that the operation was a failure. However, with some kind words and encouragement from Liz, Manya discovers for herself that she can experience sexual pleasure.
When chronic cosmetic surgery patient Mrs. Hedda Grubman returns with another frivolous demand, Sean and Christian finally refuse to do anything further to her. But they take pity when she tells them that her daughter has recently been diagnosed with cancer and confesses her own debilitating need to appear young and strong in order to support her daughter. After reluctantly agreeing to perform one last surgery, the doctors experience major problems with Mrs. Grubman's overtaxed body, and the aftermath leads to a lot of soul searching for all involved.
While driving home, Sean is broadsided by another car and rushed to the hospital. He was saved from major injury by his vehicle's safety devices, but his view of life has changed. Inspired by a patient, Joel Gideon, who suffered severe frostbite trying to conquer Mount Everest, Sean plans a shark-diving trip with Matt. Sean intends to prove to Matt - and himself - that he is not a wimp, but when a tragedy occurs on the boat before they can even get into the water, Sean ends up impressing Matt for much more important reasons.
An unlikely alliance forms between middle-aged anesthesiologist Liz, a lesbian longing to get pregnant but unable to find a suitable sperm donor, and unfulfilled Christian, who deeply misses being a father. Sean feels guilty after an eager older patient, Bobbi Broderick, who didn't fully comprehend the ramifications of liposuction overreacts to the ugly immediate aftermath.
Sean and Christian are moved by the plight of a budding model whose face has been brutally disfigured by a serial rapist. They call her in and repair her face at no charge. Guiltily and reluctantly going along with a plan initiated by Christian, Sean also convinces the victim to allow the surgery to be recorded by the news crew to deflect Bobbi's slanderous efforts. But when Bobbi arrives during the taping of a post-operation interview, the situation comes to a surprising climax.
When a homeless prostitute, Agatha Ripp, arrives at McNamara/Troy, the doctors fear she simply wants pro bono surgery for scars on her wrists. But she tells Christian and Sean that she is being deified by a devout parish of Christians because her injuries resemble the stigmata, the wounds Jesus Christ suffered on the cross. She asks them to reveal to everyone that she caused the injuries herself and is not a spiritual leader.
Sean's life is in ruins after learning that Christian is Matt's biological father due to a premarital tryst with Julia. He ejects Julia from their house and demands the dissolution of his partnership with Christian. But the two devastated men must first make a business trip to a New York university to separate adult conjoined twins, Rose and Raven Rosenberg in a historic operation.
Having tenuously reconciled and agreed to continue their partnership, Sean and Christian consult with an exuberant newspaper journalist, Ike Connors, who wants breast implants for himself. After painfully watching his loving wife, Amy, suffer through breast cancer, a mastectomy and subsequent implant surgery, Ike wants to experience the trauma for himself and live with breasts for a year, during which he will write a book about it, the proceeds of which he will donate to a cancer care center.
While the doctors work with an expert ocularist to create and implant artificial eyes for a beautiful blind woman, Natasha Charles, Christian finds himself drawn to Natasha's direct and disarming sensuality. When Natasha makes a date with a man she corresponded with via the Internet, Christian worries that she will fall prey to selfish males like himself - but as his attraction to her grows, Christian discovers that not being able to use his good looks to get what he wants puts him in a vulnerable position.
After taking too many painkillers and drinking alcohol, Julia has fallen through a glass door, severely damaging her face. At first, Sean refuses to operate on her, still bitter that she recently went to a rival plastic surgeon and got breast implants. But knowing that he is the most skilled doctor in town and finally allowing himself a modicum of sympathy for his emotionally disintegrating wife, Sean relents. He and Christian repair Julia's facial injuries and, as she requests, remove the breast implants.
When a poor Latina woman arrives in Sean and Christian's office with horrible blisters on her forehead, the doctors learn that their old associate, Merrill Bobolit, is performing cheap, illegal cosmetic surgery on poverty-stricken people. Feeling guilty because he had reported Bobolit's past indiscretions, which led to Bobolit losing his license, Christian tracks him down and finds the drug-addled surgeon operating out of the back room of a dingy nail salon. As Christian sponsors Bobolit in a 12-step program, the two colleagues bond. But when Christian misses a meeting with Bobolit because of a surgery, the desperate man has a relapse, with terrible consequences for one of Bobolit's misguided patients - and for Christian.
Sean and Christian reluctantly accept the case of Trudy Nye, who wants her nose fixed. Years ago, her abusive husband broke it - on the same day he killed their young son in anger. Now he is getting out of prison early. When Trudy comes back - accompanied by her husband, who swears he is repentant - and he asks for cosmetic surgery for himself, the doctors must make a hard decision.
Sean has been operating pro bono on victims of The Carver, a serial rapist who chooses good-looking people and carves their faces as a message to society about beauty and conformity. After repairing the face of a male model, The Carver's latest victim, Sean attracts the attention of the newswoman who publicized the recent ordeal of Naomi Gaines. But Sean's television exposure has terrible consequences.
Celebrity Joan Rivers, who is famous for having undergone many cosmetic surgeries, consults with the doctors. However, what Joan requests astonishes even Sean and Christian.