Hepatitis C virus (HCV) is a hepatotropic RNA virus that causes acute and chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. It is widely accepted that cellular immune responses play an important role in viral clearance and disease pathogenesis. However, HCV often evades effective immune recognition and has a propensity to persist in the majority of acutely infected individuals (ca. 80%). The immunological and virological basis for the inefficiency of the cellular immune response to clear or control the virus is not known. Recent studies, however, have provided new insights into the mechanisms of viral clearance and persistence that will be discussed in detail.