After a group of reapers, responsible for extracting souls from the dying, lose their leader and mentor, they are given a new boss who emphasizes efficiency and enjoying life to the fullest. As they begin to break the rules and discover their own desires, George, the narrator and one of the reapers, finds herself at a crossroads when she is fired from her temp job and struggles to connect with her sister. With their new boss showing them that nothing they do matters, the reapers start to question their purpose in life after death.

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Some movies that have similar genres and were produced around the same time as Dead Like Me: Life After Death include TiMER, The Secret Life of Walter Mitty, The Cobbler, Ghost Town, Ricky, Ruby Sparks.