Since the discovery of the hepatitis C virus (HCV), it has become evident that this infectious agent is a primary cause of posttransfusion and sporadic non-A, non-B hepatitis. Identification and introduction of surrogate markers for posttransfusion hepatitis and later introduction of anti-HCV screening has decreased the incidence of posttransfusion hepatitis. Community-acquired HCV infection is less common than posttransfusion HCV hepatitis. HCV infection may lead to liver cirrhosis without prior evidence of laboratory or histologic infection. Populations at risk for HCV infection include patients receiving organ transplants, health care workers, infants born to HCV-infected mothers, and hemodialysis patients. Intravenous drug abusers and their sexual partners also demonstrate a high rate of HCV infection. Nosocomial HCV transmission may occur despite the observance of universal precautions. Dental or surgical intervention, salivary inoculation, family members infected with HCV, cocaine abuse, HIV infection, and lower socioeconomic status also each correlate with an increased risk of infection. HCV infection is associated with many immune-mediated diseases. There may also be some relationship between human leukocyte antigens and HCV infection. Since there currently is no HCV vaccine, prevention of exposure remains the only possibility for reducing HCV transmission and prevalence.