Although the incidence of hepatitis C virus (HCV) is declining, a large reservoir of patients with chronic hepatitis C exists. Unless effective HCV antiviral regimens are developed, many patients with asymptomatic HCV will develop clinical symptoms in the next 15 to 20 years. Mood disorders are common in patients with HCV referred for psychiatric consultation. Interferon is the primary treatment for chronic hepatitis C but can induce depression and other mental and neuropsychiatric syndromes. Mood disorders associated with hepatitis C may respond to psychiatric intervention. Psychiatrists need to be aware of the clinical issues in the diagnosis and treatment of depression complicating chronic hepatitis C.