AIMS: To examine the evidence for excluding chronic hepatitis C (CHC) patients with substance abuse from treatment with interferon (IFN) and ribavirin. METHODS: We reviewed clinical trials focussing on the treatment of chronic hepatitis C of patients with substance abuse between 2001 and 2004. Ten clinical trials concerning antiviral treatment in substance abusers were described of which six were controlled ones. There were no randomised trials. There was one controlled multi-centre trial. One trial used pegylated IFN. RESULTS: In the total group of substance abusers the sustained viral response (SVR) and the adherence was not different from control groups. In former drug users, active drug users and patients taking substitution therapy for opioid dependence the sustained viral response and adherence was not different from control populations. However, non-substituted active drug users seemed more likely to be lost to follow-up. Discontinuation of treatment occurred most frequently during the first 8 weeks of therapy. Neurobehavioural changes leading to depression started in the first 8 weeks of treatment. Although follow-up periods after SVR were short, the currently described re-infection rate occurring in active intravenous drug users remains low. CONCLUSIONS: There is no evidence to withhold antiviral treatment against HCV in active substance abusers. It seems important to advise to start substitution therapy in non-substituted active drug users, increase substitution therapy dose in substituted patients and treat depression as early as possible. More prospective controlled trials on HCV treatment in active and difficult-to-reach substance users are needed.