Several large, randomized, controlled treatment trials in persons with hepatitis C and ongoing hepatitis have been reported recently. These have shown that, in patients without other comorbid conditions, treatment for from 6 to 12 months with a combination of interferon-alpha 2b, 3 MU three times a week (ttw), plus ribavirin, 1,000-1,200 mg daily, results in a higher incidence of sustained virologic response than does treatment with interferon-alpha 2b monotherapy, 3 MU ttw, given for similar durations. Patients who have relapsed after interferon monotherapy may achieve a sustained virologic response when retreated with interferon plus ribavirin for 6 months or when given a higher dose of interferon for a longer duration than the initial treatment. By contrast, patients who had no virologic response to prior interferon monotherapy have only a small chance of achieving a sustained response when similarly retreated. Although the efficacy of treatment for hepatitis C has improved steadily over the last decade, current interferon-based therapies still achieve a sustained virologic response in fewer than half of patients who initiate therapy, are associated with appreciable side effects, and are expensive. Furthermore, the natural history of chronic hepatitis C suggests that even in the absence of therapy, most patients with chronic hepatitis C infection may experience little morbidity or mortality for decades. Finally, published therapeutic trials stem largely from tertiary referral centers, where an especially high level of commitment is expected from both the patients and the team in charge of therapy. Typically, such trials have also excluded patients with comorbid diseases, thus reducing their "generalizability." This review focuses on two fundamental questions about the currently available treatments for this disease: Who should be treated with them? And when should they be treated? Critical analysis suggests that the answers to these questions are not as clear as they may superficially appear.