Hepatitis C virus (HCV) infection is most often clinically inapparent and rarely associated with symptoms of acute hepatitis. Most patients, however, fail to resolve the acute infection and proceed to develop chronic hepatitis with the risk of liver cirrhosis and hepatocellular carcinoma later in life. Since the kinetics of the earliest events of virus–host interaction are likely to determine the outcome of infection, research has focused on the characterization of the strength and kinetics of the antiviral immune response in different stages of disease. The identification of the immunological correlates of viral clearance is pivotal for the development of vaccines and efficient therapies.