Before the advent of highly active antiretroviral therapy (HAART), the vast majority of HIV-infected patients died from AIDS-related diseases. But, amongst those with access to HAART, AIDS is no longer the leading cause of death. Instead, liver disease is fast becoming the commonest cause of death in HIV-infected patients, particularly in those who have a co-infection with hepatitis C (HCV). The four recent comparative trials of peginterferon and ribavirin in HIV/HCV coinfected patients have provided valuable new information about the most appropriate treatment of this difficult group of patients. As with HIV-negative patients, it is clear that peginterferon alpha has advantages over non-pegylated treatment, with superior efficacy, in the form of higher sustained virological responders and comparable safety. Discontinuation rates were higher than reported in HCV mono-infected patients but comparable for most treatment arms. Furthermore, in about half the patients, treatments were not stopped during the first months of treatment because of side effects, but due to non-early virological response.