The highest response rates to antiviral therapy for the treatment of chronic hepatitis C have been achieved using the combination of peginterferon and ribavirin. Recently completed controlled trials have reported rates of sustained virological response (SVR) between 50% and 60% in patients treated with higher doses of peginterferon and ribavirin, which was 5% to 10% higher with standard doses of interferon alfa and ribavirin. The major determinant of outcome of therapy is hepatitis C virus (HCV) genotype. With the combination of peginterferon and ribavirin, patients with genotype 1 achieve response rates of 40% to 45%, compared with rates approaching 80% with genotypes 2 or 3. Importantly, patients with HCV genotype 1 achieve higher rates of response with 48 weeks than with 24 weeks of therapy, whereas patients with genotypes 2 and 3 are adequately treated with a 24-week course. Furthermore, patients with genotypes 2 and 3 require only 800 mg of ribavirin daily to achieve optimal response rates, whereas 1,000 to 1,200 mg daily is needed for patients with genotype 1. Future studies should focus on optimizing the dose of peginterferon and ribavirin by patient characteristics, particularly on resolving the issue of weight-based dosing. For patients with good prognostic factors, a lower dose and shorter course of peginterferon may be adequate for full effect. Importantly, research is needed to show how treatment regimens can best be applied to other patient groups with hepatitis C, such as patients with acute hepatitis, human immunodeficiency virus coinfection, renal disease, solid-organ transplant, neuropyschiatric disease, autoimmunity, and alcohol or substance abuse.