1. Liver disease related to chronic viral hepatitis is the leading indication for orthotopic liver transplantation (OLT) worldwide. 2. The natural history of hepatitis B virus infection has been dramatically modified, and outcome has improved substantially in the last decade with the use of hepatitis B immunoglobulin and lamivudine. 3. Hepatitis C virus (HCV) recurrence, defined by histological injury, is almost universal, and a subset of patients (20% to 30%) develops allograft cirrhosis by the fifth year post-OLT. 4. Unfortunately, antiviral therapy for hepatitis C post-OLT, even when initiated preemptively before the development of histological recurrence in the first few weeks post-OLT, has failed to alter the natural history of HCV disease recurrence. 5. HCV-related allograft cirrhosis is associated with a high rate of decompensation and mortality.