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Under normal circumstances, absorptive and secretory processes are tightly regulated such that absorption predominates, thereby enabling conservation of the large volumes of water that pass through the intestine each day. However, in conditions of secretory diarrhea, this balance becomes dysregulated, so that fluid secretion, driven primarily by Cl<jats:sup>\u2212<\/jats:sup> secretion, overwhelms absorptive capacity, leading to increased loss of water in the stool. Secretory diarrheas are common and include those induced by pathogenic bacteria and viruses, allergens, and disruptions to bile acid homeostasis, or as a side effect of many drugs. Here, we review the cellular and molecular mechanisms by which Cl<jats:sup>\u2212<\/jats:sup> and fluid secretion in the intestine are regulated, how these mechanisms become dysregulated in conditions of secretory diarrhea, currently available and emerging therapeutic approaches, and how new strategies to exploit intestinal secretory mechanisms are successfully being used in the treatment of constipation. <\/jats:p>","DOI":"10.1152\/ajpgi.00316.2021","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T13:00:37Z","timestamp":1645016437000},"page":"G405-G420","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":99,"title":["Intestinal secretory mechanisms and diarrhea"],"prefix":"10.1152","volume":"322","author":[{"given":"Stephen J.","family":"Keely","sequence":"first","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, University of 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