The novel tells the story of three young women who become fast friends in the turbulent post-war worlds of Broadway and Hollywood: Anne Welles, a reserved New England beauty who sees New York as the romantic city of her dreams; Neely O'Hara, an ebullient vaudevillian with a talent she doesn't fully understand; and Jennifer North, a sweet-natured showgirl who wants only to be loved. As life becomes difficult, each woman grows increasingly dependent on "dolls," the amphetamines and barbiturates which, for a time, seem to help.
Crossing their paths are such people as Helen Lawson, a brilliant but ruthless Broadway legend; Lyon Burke, a magnetic but self-centered theatrical attorney; Tony Polar, a child-like but sexually aggressive pop singer; Kevin Gillmore, a powerful but lovesick cosmetics tycoon; and Ted Casablanca, a potent but opportunistic fashion designer.
Over the course of twenty eventful years (1945–1965), each of the women strives to ascend the Mount Everest of her dreams, only to find herself back in the valley of the dolls.