This review of acetaminophen hepatotoxicity begins with a history of the drug and consideration of the scope of its current use. The molecular basis for hepatotoxicity is discussed and this serves as a background for delineation of its clinical manifestations and treatment. Although massive overdose in attempted suicide remains the most common setting for hepatotoxicity from acetaminophen, its occurrence with ingestion of the drug in therapeutic quantities is being recognized increasingly. The particular susceptibility of the alcoholic individual to this complication is reviewed, and recommendations regarding more complete labelling of the drug are offered.