Hepatitis is an unusual manifestation of herpesvirus infection. Herpes simplex virus hepatitis is a difficult diagnosis to establish, and the infection is often fatal. We report one case of herpes simplex virus hepatitis and review 51 cases in the literature. Impaired immunity resulting from pregnancy, malignancy, immunosuppression, or inhalational anesthetics may be predisposing factors. Fever, nausea, vomiting, abdominal pain, leukopenia, thrombocytopenia, coagulopathy, and a marked rise in serum transaminase levels are invariably present. Liver biopsy is the procedure of choice for diagnosis. The liver appears mottled and has a minimal inflammatory response. Mortality rates associated with herpes simplex virus hepatitis are high, and early diagnosis and treatment with acyclovir or vidarabine may produce a favorable outcome.