Since the decline in HIV-related morbidity and mortality after introduction of highly active antiretroviral therapy (HAART) in 1996, liver disease caused by chronic infection with hepatitis C virus (HCV) has become an increasingly important cause of morbidity and mortality among HIV-infected patients infected parenterally with HCV in more developed countries. A third of HIV-infected individuals in Europe and the USA have HCV co-infection. HIV accelerates HCV liver disease especially when HIV-associated immunodeficiency progresses. With the introduction of pegylated interferon in combination with ribavirin, greatly improved treatment options for patients with HIV and HCV co-infection have become available and have led to sustained virological response rates of up to 40%. Furthermore, recent cohort analyses have shown that immune reconstitution induced by HAART can improve the course of hepatitis C leading to a decline in liver-related mortality. However, patients with HCV co-infection are at increased risk of hepatotoxicity from HAART. Owing to the high rates of HIV and HCV co-infection worldwide, new improved treatment strategies and guidelines for the management of co-infection remain a major future goal.