“Intestinal failure” (IF) is the term used to describe a condition in which the gastrointestinal tract can no longer support nutritional needs with enteral supplements and there is a need for intravenous (IV) support including for the delivery of hydration, electrolytes, or parenteral nutrition (PN). Despite many potential causes of IF, short bowel syndrome (SBS) is a common etiologic factor. Even with significant advances in PN-related therapy including availability of intravenous lipid emulsions (and improvements in the care of vascular access devices, liver disease continues to be of concern. This review highlights the nutritional and medical management of IF with a focus on IF or PN-associated liver disease in SBS.