Duloxetine hydrochloride was approved by the Food and Drug Administration in August 2004 for the treatment of major depressive disorder and diabetic peripheral neuropathic pain. Initial product labeling contained a precaution regarding the risk for increases in liver function test results. Recently, postmarketing research has revealed episodes of cholestatic jaundice and increases in transaminase levels to greater than 20 times normal in patients with chronic liver disease.In this case report, we describe a patient with non-Hodgkin's lymphoma in remission and depression treated with duloxetine and mirtazapine.Approximately 6 weeks after increasing her duloxetine dose from 30 to 60 mg daily, she became jaundiced and presented with fulminant hepatic failure. Liver function tests immediately before initiating duloxetine were not available, although the patient carried no prior history of chronic liver disease. A complete work-up for alternate causes failed to reveal another explanation for the patient's clinical presentation. A liver biopsy examination showed histologic changes of subacute injury and the patient's clinical course was consistent with drug-induced liver injury. Despite aggressive measures, the patient's condition deteriorated and the decision was made to withdraw care.This report shows a case of fulminant hepatic failure and death involving duloxetine use. Given recent reports of severe hepatotoxicity associated with the use of duloxetine in patients with pre-existing liver disease, further investigation into the safety of this compound is warranted.