Prospective, randomized, controlled, phase 3 clinical trials establish pegylated interferon (PEG-IFN) alfa plus ribavirin as the standard of care for patients with chronic hepatitis C. Such clinical trials are conducted in a highly regimented manner; patients must meet strict inclusion/exclusion criteria, and treatment is administered under rigid protocols with close monitoring by study personnel. Whether the results of phase 3 trials can be generalized or achieved in everyday clinical practice is questioned in several therapeutic areas. The efficacy of PEG-IFN alfa plus ribavirin therapy observed in pivotal phase 3 trials has been confirmed in several community-based trials conducted in North America and Europe, demonstrating consistent overall rates of sustained virologic response across a wide range of patient populations. Sustained virologic response rates stratified by genotype, viral load, fibrosis score, age, and ethnicity, factors known to impact treatment outcome, are consistent between these trials and comparable to those reported in clinical trials. The United States-based WIN-R trial confirmed the value of combining weight-based ribavirin dosing with weight-based PEG-IFN alfa-2b dosing across a spectrum of patient body weights. Large Canadian trials (POWeR and EAP), a German trial (AWB), a French study (Hepatys), and an Italian study demonstrated that PEG-IFN alfa plus ribavirin produces excellent efficacy in difficult-to-treat patient populations. Collectively, these results confirm the efficacy of current standard treatment regimens in a wide range of community-based settings, affording clinicians confidence that they can attain results similar to those of rigidly controlled randomized trials.