Recent advances in antiretroviral therapy for HIV infection have substantially improved overall mortality, as well as morbidity from life-threatening opportunistic infections. In place of the usual HIV-associated opportunistic infections, morbidity and mortality due to the sequelae of hepatitis B (HBV) and C virus (HCV) infections have taken on a leading role in HIV-infected individuals. This review will examine the pathogenesis of these viruses in the setting of co-infection and the effect of immunosuppression with HIV, the natural history of co-infection, with particular attention to the effect on serological and histological markers, and the effect of immune reconstitution on the course of HBV and HCV infection. Consideration will also be given to the effect of HIV infection on HBV and HCV load (especially for HCV) and progression of liver disease. Finally, we will discuss the rapidly evolving area of therapy, with particular attention to many of the newer agents now in clinical trials, as well as combinations of these agents.