Hepatitis C virus (HCV) has become the leading indication for liver transplantation (LT) worldwide. Short-term graft and patient survival after LT in these individuals is comparable with other indications for LT. There is, however, a disturbing trend for decreased survival over the longer term. The natural history of HCV infection after LT is evolving. Its early recurrence and the wide spectrum of recurrent disease is recognized, from minimal histological and clinical disease to very aggressive forms of hepatic damage such as fibrosing cholestatic hepatitis. There is growing concern that recurrent HCV is becoming more aggressive. Although many factors have been implicated, the causes have not been fully elucidated. Interferon-based antiviral therapy is challenging to use in this patient population because of significant toxicity. Nevertheless, these agents have some efficacy, and pegylated interferons, which are now being used more frequently, achieve superior response rates. The role of liver retransplantation in this patient population is controversial, because of both a reduced survival rate and an overall shortage of organ donors. The present review discusses the challenges that occur in LT recipients with HCV.