The approval of the first protease inhibitors as treatment for hepatitis C virus (HCV) infection is rapidly transforming the way patients with chronic hepatitis C are managed. Treatment regimens are moving to combinations given for shortened periods, excluding poorly tolerated subcutaneous interferon, and providing rates of cure exceeding 75%. The recognition of HCV infection as a systemic disease, not limited to producing liver damage, in which extrahepatic complications play a major role as the cause of morbidity and mortality, is prompting the treatment of a growing number of HCV-infected individuals. However, new challenges are emerging, including the need to diagnose a substantial proportion of asymptomatic carriers, the risk of potentially harmful drug-drug interactions and the high cost of medications. The future will probably see a progressive marginalization of residual HCV populations, with increasing over-representation of illegal immigrants, alcohol abusers, intravenous drug users and the mentally disabled.