Cirrhosis due to chronic hepatitis C is now the leading indication for liver transplantation in the United States. Current data from existing clinical trials suggest that 41% of patients with genotype 1 hepatitis C virus infection (HCV) and 73% with genotype 2 or 3 infection with advanced fibrosis or early compensated cirrhosis can achieve sustained virologic response (SVR) to antiviral therapy. However, response to therapy declines with severity of liver disease and nonresponse to prior interferon-based regimens. Although SVR rates are low in patients with decompensated cirrhosis, on-treatment clearance of HCV from blood occurs in about 30% of those with genotype 1 infection and 80% of those with genotype 2 or 3. In addition, recent reports suggest that pretransplantation clearance of HCV RNA from blood may reduce the risk of HCV recurrence after transplantation. In the absence of a virologic cure, maintenance therapy with peginterferon may slow disease progression and reduce the rate of clinical decompensation.