Injection drug use (IDU) accounts for 75% of incident cases of hepatitis C virus (HCV) infection in the developed world. Of those infected with HCV, up to 80% will go on to develop chronic disease. Intervention with effective treatment in eligible subjects will limit the impact of the long-term consequences of infection. The use of combination therapy with pegylated interferon and ribavirin may lead to a cure in up to 80% of treated individuals who carry genotype 2 or 3 isolates. Such individuals account for up to 45% of certain cohorts, such as in the inner city of Vancouver. Historically, many IDUs have not received treatment for HCV infection even if it were medically indicated. Recent data (including our own) suggest that, in the right context, response rates similar to those reported in clinical trials of HCV therapy can be achieved in IDUs, even with ongoing drug use. This is all the more important given that prior infection may protect against re-infection even in the presence of ongoing risk behaviors for HCV transmission. The keys to a successful program appear to be appropriate patient selection as well as the delivery of care within an appropriate setting, preferably with a multidisciplinary team in a way that addresses the issue of addiction and other conditions simultaneously. The development of such programs may be quite complex, but the ultimate benefit (for the treated population and for society as a whole) is certainly worth the effort.