Total parenteral nutrition (TPN) was first established as a life-saving approach for nutritional support in infants in 1968. Originally, the solution contained only dextrose, amino acids, minerals, and vitamins, as there were no suitable lipid solutions. To overcome this limitation, plasma was given to provide essential fatty acids. However, high carbohydrate administration during TPN can increase hepatic de novo lipogenesis and may predispose individuals to hyperglycemia, so the initial formulations were not ideal. Lipid emulsions were created to supply the necessary essential fatty acids to prevent essential fatty acid deficiency (EFAD) and to the meet energy and growth needs. While the provision of TPN containing lipid emulsions has successfully reduced the overall mortality of premature infants and infants that are intractable to enteral feeding, there have been a number of diseases that have arisen from its use. Despite line infections and sepsis being the most common issues with TPN, more complex diseases can arise during TPN use. Cholestatic liver disease historically has been among the common TPN related morbidities in infants.