In the Western world, most people infected with the hepatitis C virus (HCV) have used illicit drugs and very likely have been infected after having shared needles and other drug-related paraphernalia. Although many such individuals have ceased to use drugs, a substantial proportion of HCV-positive patients continue to inject themselves, and their high-risk behavior is responsible for the current continuous spread of HCV in developed countries, where approximately 5 of 6 new infections occur in intravenous drug users. The appropriate management of HCV infection in that setting is of the utmost importance from a public health perspective (and even though no evidence-based studies have shown the cost-effectiveness of treating active drug users). The morbidity of HCV-infected drug users is complicated by the frequent occurrence of cofactors that accelerate the progression of liver disease, such as alcohol and cannabis use and coinfection with the human immunodeficiency virus or the hepatitis B virus. Within a decade, former drug users may account for most candidates for liver transplant, unless the progression of hepatitis can be halted by successful antiviral therapy. Although many patients infected with HCV are young and are often infected with the relatively easy-to-treat genotype 3a, barriers to antiviral therapy are significant and multifaceted. They include low acceptability among patients, little willingness among physicians to provide antiviral treatment to active drug users, fear of difficulties in managing the adverse effects associated with pegylated interferon-alfa and ribavirin therapy, and the perceived risk of reinfection after successful treatment. Most other hurdles can now be successfully overcome by a multidisciplinary approach that consists of integrating the support of specialists in infectious diseases, hepatology, psychiatry, and substance abuse with that of specifically trained paramedics. I trust that the reader will be convinced of the feasibility of antiviral therapy in a setting in which decision making has been characterized – for too long a time – by moral overtones rather than by scientific evidence.