Chronic hepatitis C virus (HCV) infection is common and often asymptomatic. Antibodies against HCV are a highly sensitive marker of infection. Molecular testing for HCV is used to confirm a positive result on antibody testing and to provide prognostic information for treatment; however, quantitative HCV RNA does not correlate with disease severity or risk for progression. Chronic HCV infection is most frequently associated with remote or current intravenous drug use and blood transfusion before 1992, although as many as 20% of infected patients have no identifiable risk factor. In an estimated 15% to 20% of persons infected with HCV, the infection progresses to cirrhosis; alcohol intake is an important cofactor in this progression. Most specialists prefer to include an examination of liver histology in the management of patients with chronic HCV infection to aid prognostic and treatment decisions. The current standard of pharmacologic treatment of chronic HCV is weekly subcutaneous peginterferon in combination with daily oral ribavirin, which results in sustained virologic response in approximately 55% of chronically infected patients. Side effects of interferon therapy include myalgias, fever, nausea, irritability, and depression. The cost-effectiveness of interferon therapy is similar to that of many commonly accepted medical interventions. The primary care physician serves a vital role in identifying patients with chronic HCV infection, educating patients about risk factors for transmission, advising patients about the avoidance of alcohol, and aiding patients in making treatment decisions.