Hepatitis C-associated liver failure is the most common indication for liver transplantation and the infection recurs nearly universally following transplantation. Histologic evidence of recurrence is apparent in approximately 50% of HCV-infected recipients in the first postoperative year. Approximately 10% of HCV-infected recipients will die or lose their allograft secondary to hepatitis C-associated allograft failure in the medium term. HCV-infected recipients who undergo retransplantation experience 5-year patient and graft survival rates that are similar to recipients undergoing retransplantation who are not HCV-infected. While the choice of calcineurin inhibitor or the use of azathioprine have not been clearly shown to affect histologic recurrence of hepatitis C or the frequency of rejection in HCV-infected recipients, cumulative exposure to corticosteroids is associated with increased mortality, higher levels of HCV viremia, and more severe histologic recurrence. In contrast to non-HCV-infected recipients, treatment for acute cellular rejection is associated with attenuated patient survival among recipients with hepatitis C. The development of steroid-resistant rejection is associated with a greater than 5-fold increased risk of mortality in HCV-infected liver transplant recipients. In lieu of large studies in a posttransplant population, therapy with pegylated IFN (+/- ribavirin) should be considered in recipients with histologically apparent recurrence of hepatitis C before total bilirubin exceeds 3 mg/dl. The role of hepatitis C immunoglobulin and new immunosuppression agents in the management of posttransplant hepatitis C infection is still evolving.