Two antiviral treatments have been approved for hepatitis B virus (HBV) infection by the US Food and Drug Administration (FDA) for use in children: interferon (IFN)-alpha, 6 MU/m(2) three times a week subcutaneously for 6 months, and lamivudine, 3 mg/kg/d orally for 12 months. Twenty-six percent to 58% of children treated with IFN become HBV DNA negative, and up to 38% become negative to hepatitis B e antigen (HBeAg). Lamivudine, a nucleoside analogue that blocks viral replication by inhibition of the HBV polymerase, has been associated with comparable rates of seroconversion of HBeAg to anti-HBe. Loss of surface antigen occurs in less than 5% of patients treated with lamivudine, compared with 3% to 33% in those treated with IFN-alpha. Fifty percent to 65% of children treated with lamivudine clear HBV DNA after 12 months of therapy, but relapse rates have not been clarified. Patients treated with lamivudine develop drug-resistant (YMDD) mutants in the HBV polymerase at the rate of 16% to 32% per year. No treatments for children with hepatitis C virus (HCV) have been approved by the FDA. However, published reports describe treatment with IFN monotherapy and combination therapy with IFN and ribavirin. Trials of PEG-IFN alone or in combination with ribavirin are in progress. Given the lack of data regarding treatment of HCV in children, it is generally agreed among pediatric hepatologists that the optimal treatment is within the context of randomized, controlled trials.