Following Bill's declaration in season 1 finale, Bill and Virginia resume their professional and personal relationship - both asserting it is to further the cause of their work. Virginia breaks the news to Ethan and Bill tries to be there for Libby and their new baby but finds it hard. Bill is struggling with getting his career back on track and Virginia is still working for Dr. DePaul but hungers for more. Scully is determined to succeed in his "therapy", but Margaret will bear no more illusions in her life.
Masters begins a new job at Memorial Hospital - under Betty's terms - only to find his boss insisting he leave Virginia behind in favor of a handpicked secretary. Johnson, meanwhile, still alienated at Maternity, is torn between pressing Masters to rehire her and staying by DePaul's side as her condition worsens.
Johnson tries to cover when she and Masters are seen by Langham leaving a hotel together after an evening tryst. Later, Masters attempts to bring Johnson aboard as his assistant at his new post; and Betty tries to conceal her infertility from Gene, over Masters' objections.
After Hendricks bans Masters from using black participants in his study, Masters contacts a journalist to promote his efforts, using the debunking of sexual stereotypes as the lure. Johnson is forced to accept DePaul's choice to end her chemotherapy treatments. Gene uncovers the truth about Betty and Helen's relationship. Libby fires Coral after discovering she lied about Robert.
In the wake of Masters' discovery that Johnson has continued to have romantic relationships with other men, he becomes impotent without her knowledge and cuts off their sexual work together. He tries to keep his new clinic solvent over the course of three years by borrowing against his house, offering medical services to the hotel - and finally accepting money from his mother.
Virginia continues to impersonate a patient's case history in order to glean advice from a psychiatrist. Betty and Masters' attempt to remedy Lester's impotence by hiring a prostitute rattles him even further. Libby gets the third degree when she offers her eyewitness testimony regarding the beaten man. And Barbara Sanders wrestles with an unsettling diagnosis that exposes a chain of secrets and causes Masters and Johnson to clash over their treatment strategy.
Masters learns of a rival study and calls in a public relations expert to help brand his work with Johnson. Virginia, having finally learned of Masters' sexual difficulties, is invigorated by the prospect of finding a cure. Determined to prove her worth to Robert, Libby canvases a tenement for a rent strike. Plus, Langham is stunned when Flo informs him that he has to have sex with her in order to keep his job. And Barbara and Lester connect over their shared sexual dysfunctions.
A television crew arrives at the clinic to document Masters and Johnson's work treating sexual dysfunction. Masters considers the publicity premature, and himself unsuitable as a television presence. Virginia deals with the fallout of having prioritized her work over her parenting when George argues to take their children on a trip with his new wife. Plus, Libby finds in Robert an appreciation for what she has to offer. And Langham realizes there's no way out of his sexual contract with Flo.