There are large racial disparities in the incidence of chronic hepatitis C virus (HCV) infection in the United States. The prevalence of HCV, and the prevalence of infection with HCV genotype 1, is higher among African Americans than among other ethnic groups. African Americans also have a higher incidence of complications of HCV infection, including a higher incidence of antibodies to HCV RNA and higher incidences of occurrence of and mortality from hepatocellular carcinoma. Combination therapy with pegylated interferons and ribavirin has increased the sustained virologic response (SVR) rates, and decreased the rates and severity of adverse events, over those observed with standard interferons, with or without ribavirin, although SVR rates with peginterferons plus ribavirin are lower in African Americans than in other ethnic groups. A recent clinical trial of peginterferon alpha-2a plus ribavirin in African American patients resulted in a higher SVR rate, 26%, than observed previously, and 90% of patients showed stabilization or improvement in fibrosis. No host or viral genetic differences have yet been identified to explain the racial disparities in incidence of HCV or response to treatment, but clinical trials are currently ongoing to identify these factors. Because treatment with pegylated interferons plus ribavirin yields improved SVR rates with good tolerability, while the basis for lower response rates in African Americans is not yet known, it is recommended that all patients with chronic HCV infection, regardless of ethnic or racial background, receive combination therapy.