Hepatitis C (HCV) infection in substance addicted patients is common and represents a therapeutically challenging co-morbidity. Alcohol and perhaps other substances of abuse directly influence the natural progression of HCV disease. Concurrent mental health illness, poor socioeconomic status, and unstructured life styles are often incompatible with safe and successful delivery of HCV treatment. These issues and their effect on treatment suitability and outcome are considered in this review. Funding for HCV-addiction research and strong political backing for interventions proven to benefit those struggling with addiction are paramount to increasing access to and uptake of HCV treatment. These interventions include substance cessation programs, safe injection settings to reduce HCV incidence and multidisciplinary teams to facilitate HCV treatment provision.