All About My Mother stars Cecilia Roth as Manuela, a single mother who has lost her son Esteban on his 18th birthday. Before his death, Esteban carried a notebook everywhere he went. When Manuela would ask him what he was writing, he would answer — typically child to mother — "nothing." But Manuela reads his book after his death and discovers that he felt like half a person for never knowing his father, or even knowing who he was.

Driven by Esteban's wishes, Manuela travels from Madrid to Barcelona to search for the father and tell him for the first time that he had a son and that son is now dead. Manuela hooks up with her old friend Argrado (Antonia San Juan), a transvestite and prostitute who once lived with Manuela and her husband. One thing leads to another and Manuela finds herself working as a personal assistant to stage star Huma Rojo (Marisa Paredes), who is playing Blanche is a traveling show of A Streetcar Named Desire and is having a difficult affair with the heroin-addicted actress who plays Stella. Manuela gives up that job to care for the ill and pregnant nun Rosa (Penélope Cruz).