In patients with chronic hepatitis C who have a sustained virologic response to IFN therapy, there is a dramatic effect on the natural history of the disease, with ALT levels becoming normal, histologic activity improving or disappearing, and the progression of fibrosis slowing. A sustained virologic response 6 months after the end of treatment is predictive of a sustained remission 4 years later. From these results, a long-term survival benefit is expected from IFN treatment in patients with an intermediate or rapid rate of fibrosis. For patients with chronic hepatitis C who do not experience a sustained eradication of virus, there is evidence that IFN treatment significantly reduces the viral load and serum ALT level, improves histologic activity, and blocks fibrosis progression, in comparison with the natural history of this disease. Therefore, patients who still have a detectable level of HCV RNA should no longer be considered nonresponders to IFN therapy. Although the number of randomized trials is [figure: see text] small, cumulative data suggest that IFN therapy can reduce the incidence of and the mortality from hepatocellular carcinoma in patients with cirrhosis.