To review the virology, epidemiology, pathogenesis, natural history, clinical manifestations, and current treatment of hepatitis C virus (HCV) infection. The MEDLINE database (1966 to 1996) was searched for English-language articles and abstracts on HCV and non-A, non-B hepatitis. Papers cited in relevant primary articles were also reviewed. More than 500 original and review articles were evaluated, and the most relevant were selected. Data were extracted and reviewed by all authors. In most patients, HCV infection results in chronic hepatitis. The disease is insidious and subclinical but may progress over decades into end-stage liver disease and hepatocellular carcinoma, which makes HCV cirrhosis a leading indication for orthotopic liver transplantation. Current diagnostic methods are highly sensitive and specific, and quantitative assessment of viral load may help to predict and monitor response to treatment. The only available therapeutic option is interferon, and this agent is effective in only a small subset of patients. Infection with HCV is a significant public health problem that has important clinical and financial consequences. The tailoring of specific therapy according to viral load or genotype, better patient selection, and use of combination drug regimens may improve the chance of viral clearance and sustained biochemical and histologic response. Further understanding of the basic virology of HCV and the exact mechanisms of viral persistence and tissue injury is needed to help define future therapeutic and preventive strategies.