Diarrhea associated with short bowel syndrome (SBS) can have multiple etiologies, including accelerated intestinal transit, gastric acid hypersecretion, intestinal bacterial overgrowth, and malabsorption of fats and bile salts. As a result, patients may need multiple medications to effectively control fecal output. The armamentarium of antidiarrheal drugs includes antimotility agents, antisecretory drugs, antibiotics and probiotics, bile acid-binding resins, and pancreatic enzymes. An antidiarrheal regimen must be individualized for each patient and should be developed using a methodical, stepwise approach. Treatment should be initiated with a single first-line medication at the low end of its dosing range. Dosage and/or dosing frequency can then be slowly escalated to achieve maximal effect while minimizing adverse events. If diarrhea remains poorly controlled, additional agents can be incorporated sequentially. If modification of the regimen is required, a single medication should be altered or exchanged at a time. After each adjustment of the regimen, sufficient time should be permitted to fully assess response (≥3-5 days) before initiating additional changes. SBS-associated malabsorption is a major obstacle to optimization of an antidiarrheal regimen because drug absorption is impaired. Patients may benefit from high dosages and/or frequent dosing intervals, liquid preparations, or nonoral routes of drug delivery. Although the diarrhea associated with SBS can be debilitating, effective pharmaceutical management has the potential to substantially improve health outcomes and quality of life for these patients.

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