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Hepatitis C virus (HCV) is the main etiologic factor of post-transfusional and sporadic hepatitis, called non-A non-B in the past. These infections are characterized by a very high number of chronic carriers always with a persistent viral increase, but often at a slow pace. The seriousness of liver disease differs from one individual to another, varying from an asymptomatic form with minor or no liver injuries, to cirrhosis and hepatocellular carcinoma. Physiopathological mechanisms involved in liver injuries are still poorly understood. The direct role of immune response and of possible genetic factors is still under study. This review aims at summing up the discovery of HCV, its structure, and its variability in the various genome regions in the same individual and from one individual to another. The different methods and techniques to analyze this variability are also reviewed, as well as the various suggested ways of classifying the different types. The geographical distribution and both clinical and biological consequences of this variability are also discussed.