Identification and diagnosis of the infecting agent responsible for hepatitis C have only recently occurred. Recognition of an infecting agent distinct from that resulting in hepatitis A or B was made approximately 50 years ago. However, the ability to screen and detect this agent was possible only after molecular biology studies which led to the cloning of parts of the hepatitis C virus (HCV) and the development of a diagnostic antibody test reported by Michael Houghton and colleagues in 1989. The discovery and cloning of HCV has led to a greater understanding of its relationship to acute and chronic hepatitis, cirrhosis, primary liver cancer, and extrahepatic conditions including essential cryoglobulinemia, glomerulonephritis, and serum autoantibody positivity. New antibody tests and quantitation of HCV-RNA have allowed better diagnosis of infectivity and monitoring of treatment effects. HCV genotypes are being related to the natural history of the disease and the effects of treatment. Research continues on HCV hepatitis and other newly identified viral hepatitis agents.