Hepatitis C virus (HCV) infection is associated with a wide spectrum of liver disease ranging from asymptomatic carriage to severe forms of chronic hepatitis. HCV is not invariably pathogenic and genetic heterogeneity of HCV could be a major cause of such a variability. In clinical practice this means that presence and replication of the virus do not invariably imply a virus-induced liver damage. IgM antibodies that are the best diagnostic tools for the other forms of viral hepatitis are not sensitive and specific enough for hepatitis C, therefore we have to look for alternatives. Detection of anti-HCV does not help to distinguish past from present infections and only anti-HCV seroconversion in previously negative patients can indicate a recent HCV infection. However, the significant association between serum anti-C100-3 and HCV-RNA suggests that anti-HCV can be considered an indirect marker of HCV infectivity. In anti-HCV-negative infections and early acute hepatitis cases HCV-RNA detection will represent a valid diagnostic alternative. In patients undergoing antiviral therapy monitoring anti-HCV by immunoblotting assays and HCV-RNA by quantitative assays represent a valid tool to predict response that invariably has occurred in patients who had undetectable serum HCV-RNA and/or decreasing anti-HCV titres. Assays that detect multiple anti-HCV antibodies all together appear unsuitable for monitoring because they miss the disappearance of single antibodies. Anti-C22 appears the most frequent and earliest to be detected and usually it has the highest titre. Anti-C100 titres decrease earlier than anti-C33 and anti-C22 in patients with chronic HCV hepatitis who respond to antiviral therapy. The natural course of HCV infection appears to be characterized by three consecutive phases: disease, asymptomatic carrier and recovery. If transition from the first to the last occurs very slowly or the disease phase persists for years it may warrant in susceptible hosts severe forms of liver disease.