Parenteral nutrition associated cholestasis is a condition that challenges even the most astute clinician. The risk:benefit ratio of parenteral nutrition must be individualized for each neonate. The dilemma is based on weighing the risk of progressive cholestasis and its complications against the risk of starvation, malnutrition, and their consequences. Avoiding excessive nutrient infusion and providing even minimal enteral calories may prevent or mitigate cholestasis. Routine monitoring of hepatic function in all neonates receiving parenteral nutrition allows early detection and intervention. Affected infants must be evaluated for treatable causes of neonatal cholestasis. Parenteral nutrition related cholestasis remains a diagnosis of exclusion. Further research is needed to unravel the cause and to define the long-term consequences of parenteral nutrition associated cholestasis.