Antiviral therapy for patients with chronic hepatitis C and compensated cirrhosis, decompensated cirrhosis, or patients on the waiting list for liver transplantation is evolving. An algorithm suggesting one approach is provided (Fig. 1). Current data from existing clinical trials suggest that 41% of patients with genotype 1 HCV and 73% with genotypes 2 and 3 HCV with advanced fibrosis or early compensated cirrhosis can achieve SVR. These results have prompted many to advocate aggressive therapy in well-compensated cirrhotics (CTP Class A) who lack evidence of clinical decompensation. However, response of cirrhotics to antiviral therapy declines with severity of liver disease and nonresponse to prior interferon-based treatments. In a single center experience of treatment of decompensated cirrhotics with genotype 1 HCV, SVR was only 11%. In contrast, SVR in genotypes 2 and 3 was 50%. Reasons for low SVR in decompensated cirrhotics include high prevalence of genotype 1 HCV, inability to achieve full doses of interferon and ribavirin due to side effects and dose-limiting cytopenias, and risk of complications related to deteriorating liver function. Although SVR rates are low in decompensated cirrhotics, on-treatment clearance of HCV from blood occurs in approximately 30% of genotype 1 patients and 80% of genotype 2 and 3 patients treated with nonpegylated interferon plus ribavirin. In addition, three reports suggest that pretransplant clearance of HCV RNA from blood may reduce risk of post-transplant recurrence of hepatitis C. Carefully controlled trials of antiviral therapy in decompensated cirrhosis to define safety and efficacy are needed. In the absence of virologic cure, maintenance therapy with peginterferon may slow disease progression and reduce rate of clinical decompensation. The results of three large trials of maintenance therapy are anxiously awaited. Until the results from these maintenance trials become available, it may be reasonable to consider maintenance treatment for patients with advanced fibrosis or cirrhosis who experienced virologic relapse after cessation of combination therapy, or those who had significant viral suppression or biochemical response on combination therapy. © 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.