Recommendations for treatment of hepatitis C in patients with cirrhosis are difficult. Few prospective studies have focused on treatment of patients with advanced disease, and response rates appear to be lower and serious side effects more frequent in patients with cirrhosis. In patients with compensated cirrhosis, combination therapy with interferon alfa (3 million units [MU] 3 times a week) and ribavirin (1,000 or 1,200 mg/d) results in a sustained virological response (SVR) in 33% to 41% of patients. Responses to combination therapy are not significantly higher using peginterferon alfa 2a (180 microg/wk; 43%) or peginterferon alfa 2b (1.5 microg /kg/wk; 44%) compared with standard interferon. In using peginterferon in combination therapy, the benefits of once weekly dosing need to be weighed against the higher risks of cytopenias and greater costs with the pegylated formulations. Combination therapy results in some degree of histological improvement even in patients who are virological non-responders. These findings provide the scientific basis for ongoing studies of maintenance therapy with peginterferon to prevent complications of cirrhosis in non-responder patients with hepatitis C. Recommendations for management of decompensated cirrhosis and of recurrent hepatitis C after liver transplantation are difficult because of limitations of data, most of which are derived from uncontrolled case series. Combination therapy is poorly tolerated in both groups and rates of response are low. Thus, while the medical need is great, treatment of patients with decompensated cirrhosis or with recurrent hepatitis C after transplantation should be undertaken cautiously and only within the confines of prospective clinical trials.