Because of shared routes of transmission, hepatitis C virus (HCV) infection is common in HIV-infected persons, who have been experiencing increasing HCV-related morbidity and mortality since the advent of effective antiretroviral therapy. Infection with HIV appears to adversely affect the outcome of hepatitis C, leading to increased viral persistence after acute infection, higher levels of viremia, and accelerated progression of HCV-related liver disease. In addition, hepatitis C may affect the course and management of HIV infection. The medical management of hepatitis C in HIV-infected persons is complicated by immune suppression, potential drug interactions and toxicities, and other forms of liver disease. In addition, there is little published experience with the safety and efficacy of the best available anti-HCV medications in HIV-infected persons. Thus, current efforts must be directed at preventing HCV and HIV infections and applying the principles learned in treating persons with either infection to manage those with both. Future efforts should include studies of the pathogenesis of HCV infection in HIV-infected persons and large, prospective studies that demonstrate the optimal management of persons co-infected with HIV and HCV. Such efforts will help to eliminate HCV-related liver disease as an emerging threat to HIV-infected persons.