Recurrent hepatitis C virus (HCV) infection after orthotopic liver transplantation (OLT) has been associated with progression to cirrhosis in approximately 20% of patients, 5 years postoperatively. Accelerated decompensation has also been noted when compared with cirrhosis in non-transplant patients. Different treatment strategies are available for recurrent HCV infection post-OLT, but efforts are hindered by the modest response rates, poor tolerability and the risk of rejection as well as graft loss. Anti-HCV immunoglobulin therapy to prevent graft infection with HCV has no established role at present but studies are ongoing. Treatment prior to transplantation in patients with decompensated cirrhosis has been evaluated but the results are too preliminary to make firm recommendations. Prophylactic interferon-based antiviral therapy in the early postoperative period to prevent graft infection was shown to have low response rates and high rates of adverse effects. Treatment of established recurrent HCV infection with combination peginterferon (pegylated interferon) and ribavirin is associated with 10-59% sustained virological response and the predictive value of a positive early virological response has been validated in the post-transplant setting. Improvement in inflammatory activity after viral eradication is well established, but fibrosis regression or stabilisation is less predictable and factors such as rejection and biliary complications may still contribute to graft loss. Most studies have initiated therapy at least 6 months postoperatively in order to optimise patient tolerance and enable the addition of ribavirin. The use of adjuvant agents to treat drug-induced neutropenia and anaemia in this population is evolving and becoming a crucial part of therapy. Determination of optimal doses of both pegylated interferon and ribavirin, and guidance on when to stop treatment, as well as improving tolerability are important steps in achieving higher response rates and minimising drug toxicity.