Chronic viral hepatitis B and C are problems of immense proportions. Interferon alfa-2b is the only agent currently approved by the U.S. Food and Drug Administration for the treatment of chronic hepatitis B and C. Initial enthusiasm for this therapy has waned with the realization that response rates are low and relapses are common. Recent studies, however, provide evidence of improved response rates with higher doses of interferon alfa-2b and the use of this agent in combination with iron reduction therapy consisting of repeated phlebotomies. Predictors of an increased likelihood of response to interferon alfa-2b therapy have also been identified, and their use may improve the cost-benefit ratio for this treatment.