Neonatal hepatobiliary disorders are now better understood due primarily to new discoveries in molecular genetics, virology, and immunology. Because they are almost always pathologic and require early intervention, the neonatologist must recognize infants with these hepatocellular and ductal cholestatic problems occurring in the first few weeks of life. This article focuses mainly on new developments regarding neonatal metabolic disorders and their potential for gene therapy; perinatal infections, especially those caused by hepatitis B virus, hepatitis C virus, and human immunodeficiency virus; and recent concepts of neonatal hepatitis and biliary atresia, including a review of predictors that influence outcome for infants undergoing Kasai portoenterostomy and liver transplantation.