Nowadays short bowel syndrome (SBS) is quite frequent, because of more aggressive surgical and medical approaches to the management of neonatal intra-addominal catastrophes. Intestinal rehabilitation can be reached in case of SBS with a strategy that merges nutritional, pharmacologic and surgical approaches to achieve the ultimate goal of enteral nutrition. Long-term clinical nutrition which combines total parenteral nutrition (TPN) and enteral nutrition is required for the adaptation process. Long-term TPN can, however, be associated with mechanical, septic and metabolic complications, most of which have been consistently reduced by a better understanding of the prerequisites for its application and by improvements in parenteral solutions. Parenteral nutrition associated cholestasis (PNAC) and liver disease (PNALD) remain indeed the most worrisome complications and bear with them a high mortality rate. Their prevention will further improve the role of TPN in patients with SBS. The etiology of PNAC and PNALD, although elusive, is thought to be multifactorial and proposed theories also include problems arising from lipid emulsions. Parenteral nutrition, that includes n-3 fatty acids, appear to diminish the extent of the inflammatory response thought to be responsible for PNAC and PNALD. This article will attempt to review the role of TPN in the rehabilitation process and discuss energy and macronutrients requirements.