Neutralizing antibodies represent a key component of immune control in many viral infections. For a long time, these antibodies were thought to play a marginal role in hepatitis C virus (HCV) infection, and that cellular immune responses are more critical in immune control. The development of model systems to study HCV entry and significant advances in our understanding of viral entry and escape, have reenergized interest in the potential of protective neutralizing antibodies against HCV. Yet further investigations are needed to completely elucidate the role of neutralizing antibodies, recent data on their clinical impact during HCV infection and recent development of monoclonal antibodies capable of neutralizing autologous and heterologousHCVstrains, represent our best hope for the development of novel therapeutic or preventive vaccine.