Treatment of short bowel syndrome (SBS) is often a difficult endeavor due to the high variability among patients with SBS in regard to remaining anatomical structure and functional capacity. Research efforts to substantiate the use of existing therapies in the treatment of SBS are ongoing, with newer developments yet to be fully explored. Current therapy for SBS begins with the implementation of a modified diet based on the presence or absence of the colon. Patients with difficulty ingesting enough nutrients and fluids for weight maintenance and fluid balance may benefit from nocturnal enteral nutrition and hydration. Those with inadequate absorptive capacity despite maximization of oral and enteral intake will need parenteral nutrition (PN) or hydration. Medications, including antisecretory agents, antidiarrheals, pancreatic enzymes, bile acid sequestrants, and antibiotics, often are useful in abating symptoms commonly associated with SBS. Growth factors, including recombinant human growth hormone and glucagon-like peptide 2, may be trialed to stimulate intestinal adaptation and enhance absorption in PN-dependent SBS patients. The gradual refinement of surgical procedures for SBS, including small bowel transplantation, has led to improved outcomes, and early referral of SBS patients to centers of excellence will optimize care.