Patients with short bowel syndrome, particularly those who are dependent on long-term parenteral nutrition, face serious clinical sequelae that can dramatically impact their quality of life and survival. Over the last few decades, innovations and refinements in nutritional, pharmacologic, and surgical therapies have improved outcomes significantly. An individualized and multidisciplinary management approach is mandatory, and this should ideally take place in specialized centers with the necessary expertise and resources to address these patients’ complex physical and psychosocial issues.