Jaundice in infancy may be physiologic or due to a pathologic cause. Fractionation of the serum bilirubin level is the first step in the evaluation. Unconjugated hyperbilirubinemia if left untreated may reach toxic levels. Primary hepatobiliary disorders, as well as infectious, toxic, genetic, and metabolic diseases, may manifest with conjugated hyperbilirubinemia. A carefully organized diagnostic evaluation in a timely fashion allows early identification of treatable disorders. Medical management of the complications of cholestatic liver disease remains a major challenge. Early surgical intervention for biliary atresia and significant advances in hepatic transplantation offer the opportunity for long-term survival for infants with previously fatal liver disorders.