The adaptive immune response plays a central role in the outcome of hepatitis C virus (HCV) infection. Indeed, spontaneous viral clearance is associated with an early neutralizing antibody response as well as vigorous and sustained HCV-specific CD4+ and CD8+ T cell responses. In persistent HCV infection, however, all three components of the antiviral adaptive immune response fail due to different viral evasion strategies. In this chapter, we will describe the components of a successful immune response against HCV and summarize the mechanisms of immune failure. We will also highlight characteristics of protective CD8+ T cell responses which is the key factor to the design of an efficacious vaccine.