See also: List of Dollhouse episodes

Eliza Dushku plays a young woman called Echo, a member of a group of people known as “Actives” or “Dolls”. The Dolls are people whose personalities and existence in the outside world have been wiped clean so they can be imprinted with any number of new personas. Contents of an imprint may include semantic memory, muscle memory, skills, and language, as appropriate for different assignments (referred to as engagements). The new persona can be an amalgam of several real people, and the end result necessarily incorporates both strengths and flaws from the template personalities. The Actives are then hired out for particular jobs, which can be anything from crimes to fantasies to the occasional good deed. On engagements, Actives are monitored internally (and remotely) by Handlers. In between engagements they are mind-wiped into a child-like state and live in a futuristic dormitory/laboratory, a hidden facility nicknamed “The Dollhouse”. The Dollhouse is located somewhere in Los Angeles and is a subsidiary of a mysterious research group known as the Rossum Corporation.

The story follows Echo, who begins, in her mind-wiped state, to become self-aware.[6][7]

The show also focuses on the employees of the mysterious “Dollhouse,” including the manager of the Dollhouse, Adelle DeWitt (Olivia Williams), Echo’s Handler Boyd Langton (Harry Lennix), and the in-house computer scientist Topher Brink (Fran Kranz), as well as two other “Dolls” named Sierra and Victor (played by Dichen Lachman and Enver Gjokaj), who are friendly with and often seem to remember Echo. The names of Actives are simply letters in the phonetic alphabet. Although the Actives are ostensibly volunteers who work for a period of five years, the operation is highly illegal and under constant threat on one end from Paul Ballard (Tahmoh Penikett), a determined federal agent who has heard a rumor about the Dolls, and on the other end a rogue Active named “Alpha”.[7]