Childhood hepatitis B virus (HBV) infection presents both medical and public health challenges. Infants who acquire HBV perinatally have up to 90% risk of developing chronic HBV infection. Many HBV-infected children have normal alanine aminotransferase values and minimal chronic hepatitis. Children with chronic HBV infection are usually asymptomatic but may develop chronic liver disease or hepatocellular carcinoma. Both interferon-alfa and lamivudine are available for the treatment of chronic hepatitis B in children, but the optimal treatment of children with chronic HBV infection is evolving as the indications, timing, efficacy, and side effects of the treatments are better understood. Universal infant vaccination has been shown to decrease the frequency of HBV infection and its sequelae. This article addresses aspects of HBV infection that are either unique to or different in children.