It appears that neonates, especially those with very low birthweights, may be at especially high risk of developing cholestasis associated with total parenteral nutrition (TPN). Within 2 weeks of starting intravenous alimentation, it would appear highly desirable to be able to start at least small enteral feedings to interrupt the physiology of fasting. Such feedings may not have to be of much nutritional benefit to improve cholestasis. Calorie and amino acid intake should be limited to the requirements of the infant being treated. Whether protection of the TPN infusate from light is of benefit remains to be determined. Drug therapies for TPN-associated cholestasis of infancy have not been proven safe or effective. Additional investigations to further clarify the pathogenesis of this syndrome, and clinical studies of prophylaxis and therapy, are needed to enhance our ability to provide nutritionally effective and metabolically safe parenteral nutrition.