Hepatitis C shares common routes of infection with hepatitis B (HBV) and the human immunodeficiency virus (HIV). It is, therefore, not surprising to find that some patients with HCV are co-infected with either HIV and/or HBV. Until recently, the effects of HIV on HCV infection have not been investigated—sadly patients with HIV died long before their liver disease became problematic. However, the development of successful therapies for HIV have led to dramatic improvements in life expectancy for patients infected with this virus and in these patients, with well controlled HIV, it is becoming clear that hepatitis C may lead to the early onset of advanced liver disease. The optimal treatment for these patients is unknown but it seems likely that combination antiviral therapy will be required. The effects of HBV on HCV are also beginning to be investigated and, again, it is clear that co-infection leads to more aggressive liver disease with the two viruses interacting in poorly defined ways to increase the rate of hepatic fibrosis. Management of combined HCV/HBV infection is still under investigation and will probably involve combination therapy.