The prevalence of depression is increased in patients with chronic hepatitis C virus (HCV) infection. Several aetiological mechanisms are thought to be involved, e.g. premorbid psychiatric disease, genetic disposition to affective disorders, socio-economic factors, stigmatization and possibly HCV neuroinfection. Evidence to support that former intravenous drug abuse increases the risk of depression is lacking. It is particularly important to diagnose and treat depression in HCV patients as it constitutes a relative contraindication to antiviral treatment and may jeopardize therapeutic outcome.