Cholestasis in neonates and infants frequently confronts pediatricians and pathologists with diagnostic problems. A specific feature of the liver in neonates is the ability to react to different causative factors with a non-specific hepatitis-like picture, the so-called neonatal hepatitis. A diagnostic discrimination of the various diseases is histologically only possible with close attention to typical morphologic features. Thus, extrahepatic biliary obstructions, such as atresia or stenosis of the hepatic duct or choledochal cysts present with portal bile duct proliferation and signs of bile retention in the neoducts. In Alagille syndrome (arteriohepatic dysplasia), however, paucity of intrahepatic bile ducts is an important diagnostic feature. Metabolic disorders, such as fructosemia and galactosemia are additionally associated with steatosis. Knowledge of the clinical course and laboratory and imaging data are necessary to make the definitive diagnosis in synopsis with the morphologic findings and requires a close co-operation between the pediatrician and the pathologist.