1. Hepatitis C virus (HCV) infection in the allograft occurs in the setting of greater viral burdens than in patients pretransplantation. 2. Viral burden is increased by such immunosuppressive therapies as corticosteroids and interleukin-2 receptor antibodies. 3. Cholestatic HCV infection occurs in the setting of very high viral load and is almost certainly induced by overimmunosuppression. It is managed best by rapid reduction in levels of immunosuppression. 4. The more common chronic hepatitic HCV disease seems to behave at the molecular/cellular level in a fashion similar to the nontransplantation setting with activation of T helper subtype 1 inflammatory, profibrotic, and proapoptotic pathways. The role of immunosuppression in the acceleration of this disease is unclear, and rapid reduction in immunosuppressive doses may be detrimental. 5. Changes to definitions of types of HCV disease recurrence, disease severity, and acute allograft rejection in the presence of HCV infection are required to improve understanding of the pathogenesis.