Pegylated interferon-alpha combined with ribavirin is the current gold standard treatment for chronic hepatitis C. Illicit drug dependence is not a rare co-morbidity among chronic hepatitis C population, what can make antiviral treatment an outmost challenge. Despite high sustained virological response rate following antiviral treatment, serious psychiatric adverse reactions may occur, like depression and suicide attempt. We report a patient with recurrent depressive disorder, previous history of suicide attempt and illicit drug dependence. We discuss the singularities and challenges of managing this patient in order to complete the antiviral treatment.