With the advent of new knowledge and technologies, the survival of critically ill premature neonates has much improved compared to the last decade. One of these is parenteral nutrition (PN). Despite the magnificent benefits, longterm PN can contribute to many life-threatening complications. The parenteral nutrition-associated liver disease comprises one of the potential complications, leading to hepatic fibrosis, cirrhosis, portal hypertension, and death if liver transplantation is not performed. Its pathophysiology is still obscure, although many offending factors have been postulated, including total caloric intake, glucose and amino acid concentration, composition of the amino acid solutions, phytosterols in lipid emulsions, infection, and lack of enteral stimulation. Because there is no specific biological marker or histopathology for this condition, the definite diagnosis is exclusively based on a history of receiving long-term PN and exclusion of other possible causes of neonatal cholestasis, most importantly biliary atresia. Recent reports using ursodeoxycholic acid and cholecystokinin-octapeptide for treatment of PN-induced cholestasis have shown promising results. However, early minimal enteral feeding and prevention of catheter-related sepsis are still the mainstay of preventive measures.