Recurrent hepatitis C virus (HCV) disease is the leading cause of graft loss in liver transplant recipients with pre-transplant HCV infection. While natural history is variable, median time to recurrent cirrhosis is less than a decade. Factors contributing to risk of recurrence and rate of fibrosis progression are only partially known. Older donor age, treatment of acute rejection, cytomegalovirus infection and high pre-transplant viral load are most consistently linked with worse outcomes. Whether these factors can be modified to positively impact on HCV disease progression is unknown. The main therapeutic approach for patients with recurrent HCV disease has been the treatment with interferon and ribavirin (RBV) once recurrent disease is documented or progressive. Efficacy is lower than in nontransplant patients and tolerability, especially of RBV, is a major limitation. Stable or improved fibrosis scores are seen in the majority of sustained responders. Optimal dose, duration and timing of treatment have not been determined. Alternative strategies under study include pre-transplant treatment of decompensated cirrhotics, preemptive antiviral therapy started within weeks of transplantation and prophylactic therapy using HCV antibodies. Ongoing studies may establish a future role for alternative treatment approaches. Additionally, limited overall efficacy of interferon-based therapy in the transplant setting highlights the urgent need for new drug therapies.