Today hepatitis C remains one of the unsolved medical problems and represents a significant proportion of the remaining deaths in the HIV population, particularly in southern Europe and the USA where the prevalence of HCV/HIV-co-infection in the HIV-population ranges from 30% to 50%. Recent trials using pegylated interferon-alfa in combination with low-dose ribavirin have achieved overall sustained response rates of up to 50%. However high discontinuation rates, adverse events associated with mitochondrial toxicities or treatment of patients with advanced cirrhosis may decrease response to treatment and result in serious adverse events. Optimising antiretroviral therapy before the start of interferon-based therapy and active management of adverse events will reduce complications and improve treatment success. As novel agents to treat chronic hepatitis C may not be accessible in the coming years on a broader scale for HIV-co-infected patients the use of higher ribavirin doses and longer treatment periods should be systematically studied to improve hepatitis C therapy in co-infected patients in the near future.