We describe, to our knowledge, the first reported case of nortriptyline-induced fulminant hepatic failure. This tricyclic antidepressant drug was taken by a postmenopausal woman for 64 days before her presentation. The absence of fever, rash, or marked eosinophilia, the predominant zone 3 necrosis with bridging, and the latent period favor a metabolic idiosyncratic reaction. The fatal outcome underscores the importance of recognizing the association and discontinuing the offending agent.