The novel focuses on the lives of its three main characters Anne Welles, Jennifer North and Neely O'Hara:
The three women become fast friends. However, over the next twenty years, the women embark on careers that bring them to the heights of fame and eventual self-destruction.
Jennifer begins a relationship with nightclub singer Tony Polar; believing his childish behavior is caused by his overprotective half-sister and manager Miriam, she persuades him to elope. She travels with him to Hollywood to pursue his career, and becomes pregnant.
Upon discovering Tony’s infidelity, Jennifer ends the relationship but chooses to keep this child. Miriam explains that Tony has a congenital brain condition that causes seizures and dementia, and will culminate in total insanity. Upon learning that the child is likely to inherit the sickness, Jennifer has an abortion, without telling anyone why. This puzzles her friends, because they know her dearest wish is to have many children on whom she can lavish the affection and approval she never had.
As Jennifer is only regarded for her body and is desperate for money, she decides to perform in French art films. Stress and smoking make her an insomniac, and she begins to use the eponymous "dolls" (barbiturates) as sleep aids, as she had during the time she was in Hit the Sky .
Jennifer returns to the United States after years in Europe, where she's gained moderate success as an actress. She meets and falls in love with a middle-aged Republican senator who has hopes of becoming President. While preparing for her wedding, she is diagnosed with breast cancer. She is told she must have a mastectomy, and that she will never be able to have children. When Jennifer speaks with the Senator, she tells him about not having children, but before she can say anything about the mastectomy he responds that he is uninterested in children. He enthuses that his love for her body, breasts especially, will sustain the relationship, and that he can't stand to think of anything happening to the "perfection" of her bosom. Unable to have children and faced with another man who only loves her for her body, Jennifer commits suicide.
Anne comes from a repressive New England town, Lawrenceville, and is determined never to return there. In her administrative job, Anne’s beauty and class gain her attention. Millionaire Allen Cooper falls for her after only six weeks of dating, and demands her hand in marriage. Not ready to settle, Anne refuses.
During an out of town trip for the debut of Hit the Sky , Anne realizes that she is in love with Lyon Burke, a lawyer at the agency. They spend a blissful year together. Lyon accompanies her to Lawrenceville to help her settle her mother's estate, and falls in love with the place, telling her he wants to live there and write novels. Anne is dead set against this, because he refuses to marry her and they part company.
Anne becomes the face of Gillian Cosmetics, and becomes romantically involved with Kevin Gillmore, the owner of the company. After 15 years, Lyon returns and approaches Anne when she is nearly married to Kevin Gillmore. She leaves Kevin for Lyon, and arranges with Henry Bellamy to create a job for Lyon to keep him in the U.S. The two eventually wed. Lyon discovers the ruse when Neely tells him because she is trying to get something she wants. Angry about the way she "emasculated" him, Lyon continues to have affairs. Though Anne stays with Lyon, she plans to raise her daughter Jennifer to be independent-minded and avoid the mistakes she made in her life with men. To cope with Lyon’s infidelity, Anne begins to take pills to sleep.
Neely O'Hara becomes famous on the Broadway scene, moves to Hollywood to work in movies, and becomes a superstar in Hollywood musicals. Her handlers demand that she lose weight. Jennifer introduces her to dolls, and she quickly becomes addicted to "uppers" (Dexedrine) to lose weight and stay awake during the day and barbiturates (Seconal, Nembutal) to sleep. The grueling, unglamorous work of being a Hollywood actress is described in detail and Neely's dependence on the pills is shown as understandable. She combines the pills and often uses alcohol to enhance their effect. Partly due to the effects of the pills, she earns a reputation as demanding, spoiled, and difficult to handle. Her movies earn high returns at the box office, but it isn't enough; the studio consistently loses money on her pictures due to her erratic behavior.
After numerous suicide attempts, a year-long black list from the entertainment world, and two failed marriages, Neely is committed to a psychiatric hospital. Upon release she works with Lyon Burke to revitalize her career, and begins an affair with him. She quickly returns to her vicious, arrogant behavior.