Alec Baldwin: Dr. Barrett Moore, a plastic surgeon who was once married to Ava Moore (the transgender woman played by Famke Janssen).
Jacqueline Bissett: James, a forceful businesswoman who earns a living via the harvesting and trafficking of human organs. She is the reason that Liz (Roma Maffia) only has a single kidney.
Jill Clayburgh: Bobby Broderick, a recently divorced woman who seeks liposuction. Turns out that she’s a borderline personality. Clayburgh received an Emmy nomination for this role.
Bradley Cooper: Aidan Stone, a famous and hedonistic TV actor who appears on the medical drama “Hearts ‘n Scalpels” (a show-within-a-show on “Nip/Tuck”). He and Sean develop an odd camaraderie.
Catherine Deneuve: Diana Lubey, a French woman who requests that her deceased lover’s ashes be put into her breast implants.
Peter Dinklage: Marlowe Sawyer, the nanny whom Sean and Julia hire after the birth of baby Connor. Julia and Marlowe have a brief affair.
Larry Hagman: Burt Landau, a wealthy businessman who is married to a much younger woman, Michelle (Sanaa Lathan). He purchases the medical practice McNamara/Troy.
Marlee Matlin: Barbara Shapiro, head of the TV network that airs “Hearts ‘n Scalpels.” She fires Aidan (Bradley Cooper), making Sean the star of the medical drama.
Alanis Morissette: Poppy, a lesbian anes-thesiologist who has an affair with Liz. Seemingly gentle and loving at first, Poppy turns out to be controlling and possessive — even insisting that Liz get plastic surgery.
Vanessa Redgrave: Erica Naughton, the mother of Julia McNamara (Joely Richardson, who is Redgrave’s daughter in real life). Erica is a well-known psychologist and book author who specializes in child psychology. Yet she’s cold, distant and manipulative toward her own daughter.
Joan Rivers: Rivers played herself. She once came to McNamara/Troy to have all of her previous plastic surgeries undone, but changes her mind.
Brooke Shields: Dr. Faith Wolper, a psychiatrist who is a love and sex addict. She becomes obsessed with Christian, and tattoos his name on her lower back.