Cholestasis is a major complication that occurs frequently in patients with the short bowel syndrome and accounts for the majority of morbidity and mortality in this group of patients. The exact cause of this condition is not known and the etiology is likely multifactorial. Many new mechanistic insights into this disease are discussed and have paved the way for future investigation. For now, prompt recognition, early initiation of enteral feeding, prevention of overfeeding with parenteral nutrition, and agents that induce bile flow may be useful to prevent this catastrophic morbidity.