Recurrent infection with HCV after liver transplantation is almost universal and is associated with substantial morbidity, mortality and graft loss. In contrast to immunocompetent individuals, HCV infection in immunosuppressed transplant recipients usually has an accelerated course. Acute hepatitis develops in approximately 75% of HCV recipients in the first six months following orthotopic liver transplantation (OLT). By the fifth postoperative year, over 80% of HCV-infected liver transplant recipients will develop histologic evidence of chronic allograft injury secondary to hepatitis C, with up to 30% developing cirrhosis. While the choice of calcineurin inhibitor has 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. Unfortunately, treatment of chronic HCV in liver transplant recipients is suboptimal. Combination therapy with interferon (pegylated and nonpegylated forms) plus ribavirin appears to provide maximum benefits. Drug therapy is usually administered for recurrent disease. No prophylactic therapy is available. Preemptive regimens offer no distinctive advantages over treatments initiated for recurrent disease. Overall, treatment is poorly tolerated, with frequent need for dose reductions, especially for cytopenias, and drug discontinuation in up to 50% of patients. Optimizing drug doses is important in maximizing sustained virologic response rates. The achieved SVR is between 33% and 42% in randomized studies treating patients with histologic recurrence and 0% to 33% when used in a preemptive protocol. The potential factors that influence this low SVR rate are: 1) high percentage of patients with genotype 1 virus; 2) high viral load at the start of treatment; 3) high percentage of prior non-responders to therapy; 4) side effects that often make the use of standard doses and duration of treatment difficult; 5) the use or not of growth factors; and 6) the effect of immunosuppression. In post-transplant patients with recurrent HCV disease, combination Peg alfa-2b or alfa-2a in standard dose and ribavirin (800-1200 mg either ab initio or as an increasing dose) regimen for 48 weeks was significantly better than no therapy, but not than any other therapy.