The prevalence of hepatitis C virus infection is higher in the African American population in comparison with Caucasians and Hispanics. The majority of African Americans are infected with genotype 1 and have a high viral load, but the rate of progression to cirrhosis is lower. After the development of cirrhosis, the chance of developing hepatocellular carcinoma is higher. African Americans have been under-represented in clinical trials, and the initial preliminary observations pointing toward a lower sustained virologic response with interferon monotherapy has been confirmed in larger studies. A lower response to antiviral therapy has been demonstrated in African Americans receiving combination interferon plus ribavirin and combination peginterferon plus ribavirin. The reasons for these differences in natural history and outcomes of therapy are not understood but are the subject of ongoing study.