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For over a decade, the importance of zinc in the treatment of acute diarrhea has been recognized. More recently, the mechanisms of action of zinc are becoming clearer. This review is focused on the new evidence on the mechanisms of action of zinc in acute diarrhea.The vast majority of data derive from in-vitro studies using intestinal cell lines or from animal model. The positive action by zinc in acute diarrhea derives from a regulation of intestinal fluid transport, mucosal integrity, immunity, gene expression, and oxidative stress. A complex homeostatic network is also able to regulate zinc status at cellular and extracellular level.All these data support the use of zinc in the treatment of acute diarrhea, but further clinical studies are needed to explore the selective effects of zinc against specific pathogens responsible for diarrhea.