Short bowel syndrome (SBS) is a rare clinical condition that often results in chronic intestinal failure (CIF) due to surgical resection of parts of the gastrointestinal tract. The surgery may be necessitated by severe complicated inflammatory bowel disease (IBD), mesenteric ischemia, or abdominal trauma. In general, SBS patients present with heterogeneous postsurgical small and/or large bowel anatomy, resulting in decreased absorptive surface area and compromised absorptive function. Oral autonomy may be ultimately acquired in some but not in all patients. In particular, irreversible CIF is associated with deficient calorie, nutrient, and fluid absorption and often requires permanent or intermittent parenteral nutrition for maintaining homeostasis of metabolism and hydration status. Handling parenteral nutrition requires individual metabolic consideration and eventually adjustment, vivid monitoring of fluid and electrolytes as well as nutritional status and accurate care and hygiene of the central venous catheter access. Long-term complications of CIF and SBS may comprise macro- or micronutrient and/or fluid deficiency, renal impairment, endocarditis, and/or intestinal failure-associated liver disease (IFALD). In addition to nutritional therapy and surgical treatment especially, glucagon-like peptide-2 (GLP-2) analogues have emerged as additional successful therapeutic options for SBS patients to promote enteral autonomy. Intestinal transplantation might be considered in patients with complicated CIF.