Clozapine-induced hepatotoxicity is not well known and is usually of no clinical significance. This report describes fatal acute fulminant liver failure caused by clozapine in a 39-year-old man with chronic paranoid schizophrenia. The hepatotoxicity of clozapine is reviewed. Asymptomatic elevation of transaminase levels is observed most commonly, affecting between 30% and 50% of patients. Icteric hepatitis is uncommon, noted in 84 of 136,000 patients (0.06%). Fatal acute fulminant hepatitis has been documented in 2 patients (0.001%). The mechanism of clozapine hepatotoxicity is unknown. Although serious toxicity is rare, prescribers of clozapine should be aware of the hepatotoxic potential.