The propensity of hepatitis C virus (HCV) to cause chronic infection and ongoing liver disease represents a challenge to the immunologist and hepatologist alike. Critically, the study of HCV has been hampered by the difficulty in studying individuals with acute HCV infection. In particular, many individuals may be asymptomatic or may not engage with healthcare facilities for social reasons. Currently, the only faithful animal model is the common chimpanzee, and researchers now have reduced access due to financial and political reasons. However, work is at hand to generate small-animal models by genetically manipulating mice to accept human tissue and human immune cells and to support HCV replication. These studies may in the future add substantially to our knowledge of immunity to HCV. However, to date our knowledge has been gained predominantly from studies of individuals with chronic HCV infection. This has been supplemented by studies of acute HCV infection and also the work in the common chimpanzee, which lends itself to longitudinal analysis of HCV infection. This chapter summarizes our current knowledge on how the immune system responds to HCV, and how HCV manages to survive the onslaughts of the innate and adaptive immune systems.