Although HCV infection in children shares some clinical features with that in adults, it is clearly different in several ways. These differences may have important implications for treatment. Some differences, such as milder disease, less frequent extrahepatic manifestations, and fewer comorbid conditions causing progression, argue against aggressive treatment in childhood. Other factors, such as less severe liver disease, shorter disease duration, possibly higher rates of sustained virologic response, and better tolerance of IFN, may be reasons to pursue treatment before advanced hepatic injury occurs. Given the relatively small number of pediatric patients with HCV infection and the gaps in the current understanding of natural history and effects of therapy in these patients, treatment should be undertaken only in clinical trials, so that careful data collection and monitoring can define more precisely the safety and efficacy of IFN therapy in children.