Intravenous drug use is a major route of hepatitis C virus (HCV) transmission. In Belgium, more than 70% of the intravenous drug users (IVDUs) are HCV seropositive. In the past, medical treatment of HCV-positive IVDUs has been controversial. However, current studies support that the anti-HCV therapy of IVDUs should be the same as in other HCV-infected patients. In prison populations, HCV screening and therapy has to be performed. Patients should be counseled about the benefits of alcohol abstinence, should be educated about safer injection techniques to avoid reinfection, and should be vaccinated to avoid hepatitis A or B co-infections. Treatment of HCV infections should not be withheld from patient populations with complicated social problems. Physicians should rather develop individual treatment and follow-up plans in order to optimize compliance in IVDUs.