Abstract: BACKGROUND: Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are the two blood-borne pathogens most commonly transmitted among injection drug users via multi-person use of syringes and other injection equipment. However, important differences exist in the epidemiology of HIV and HCV within different populations of intravenous drug users. METHOD: A literature review was carried out to summarize publications describing the epidemiology and natural history of HIV and HCV in injection drug users. RESULTS: Among injection drug users worldwide, HIV prevalence varies from <5% to >80%, with annual HIV incidence between <1% and 50%. More consistency is shown in HCV prevalence (50–90%) and incidence (10–30% per year). Host, environmental and viral factors that favor rapid spread of HCV among IDUs suggest that HCV infection in a population of injection drug users may become endemic over a relatively short period of time. Lower transmission efficiency for HIV also indicates that its spread among injection drug users may be somewhat slower. CONCLUSIONS: Successful efforts to prevent transmission of blood-borne viruses among IDUs typically result in risk reduction; however, no intervention has resulted in elimination of risk behavior. To reduce HIV transmission, risk reduction may be sufficient, whereas control of HCV may necessitate the use of injection practices that guarantee elimination of exposure to equipment contaminated with even small amounts of blood.