The infant with cholestasis presents a series of diagnostic challenges which require careful delineation. Correct diagnosis, permitting selection of appropriate management and therapy, can be made in the vast majority of patients. When the diagnosis remains obscure, exploratory surgery to distinguish intrahepatic from extrahepatic cholestasis should be performed by 60 days of age in order to provide the best possible outcome. Nevertheless, in both intrahepatic and extrahepatic cholestatic disorders, the characteristics of the original insult determine the prognosis, which may often be predicted by the early liver biopsy. When end-stage liver disease is inevitable, hepatic transplantation may be considered.