The relationships between various hepatobiliary disorders and the administration of total parenteral nutrition (TPN) were reviewed and, in particular, the role of TPN in their pathogenesis was critically evaluated. Several clinical and pathological entities including steatosis, steatohepatitis, cholestasis, and cholelithiasis have been commonly linked to TPN, and instances of chronic decompensated liver disease have been reported. However, it is concluded that it is often difficult to extricate the effects of TPN on hepatobiliary function from many other hepatotoxic factors that may be operative in these patients. Thus, whereas considerable evidence exists to support a role fro carbohydrate or calorie excess in TPN solutions in the pathogenesis of steatosis, a loss of enteric stimulation and not TPN per se may be the primary factor in the development of cholestasis, biliary sludge, and gallstones. The apparent predilection of infants to TPN-related cholestasis may be based on the relative immaturity of the neonatal biliary excretory system.