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Women account for almost one of four newly diagnosed cases of the human immunodeficiency virus (HIV) infection in the United States. It is believed that up to 20% of them are co-infected with hepatitis C virus (HCV). AIDS is now the third leading cause of death in women aged 25 to 44 years in the United States. The ability to better control the HIV infection and improve survival among the co-infected population will make managing chronic liver disease due to hepatitis C the next clinical challenge for these women. This article reviews the available data and summarizes the primary care approach to the female patient with HCV-HIV co-infection.