Injection drug use is the single most important risk factor for acquiring hepatitis C virus (HCV) infection. Injection drug users acquire this infection rapidly after initiating injection practices, and up to 90% of them are chronically infected with HCV. HCV infection is a major cause of chronic liver disease, and persons infected with HCV are at risk for chronic hepatitis, cirrhosis, and primary hepatocellular carcinoma, and they risk transmitting HCV infection to others. Preventive measures for HCV infection are limited. The heterogeneous nature of HCV and its ability to undergo rapid mutation appear to prevent the development of an effective neutralizing immune response, obstructing development of a vaccine. Prevention of HCV infection must rely on educational and programmatic efforts aimed at preventing drug use, providing substance abuse treatment for persons who inject illicit drugs, and encouraging safer injection practices. These efforts should include messages about the risk and prevention of all blood-borne pathogens, including HCV, hepatitis B virus, and human immunodeficiency virus.