Hepatitis C is a leading cause of chronic liver disease in the United States, and the prevalence of hepatitis C–associated complications is increasing. Therapy with pegylated interferon and ribavirin has become the standard of care for chronic hepatitis C; the sustained response rate for treatment-naïve patients is about 55%. If certain patients fail to achieve a 12-week treatment milestone, an early virologic response, they may be taken off treatment early, potentially sparing them from unnecessary medication. Adherence is critical for treatment success. Although side effects continue to be a hindrance to the success of therapy, agents such as growth factors and antidepressants may help patients to maintain medication dosing and complete treatment. Therapy is generally recommended for those in whom the infection is most likely to progress to cirrhosis; however, there is continued debate about the suitability of certain patients for treatment, including those with persistently normal aminotransferase levels or acute hepatitis C and nonresponders to conventional treatment. Four broad groups of investigational therapeutic agents appear promising for future therapy: modified interferons and ribavirins, immunomodulators, viral life-cycle targets, and antifibrotic agents.