Zinc has caught wide scientific attention for the conceptual promise it has to offer for prevention, control and treatment of acute diarrhea. This review focuses on the mechanisms by which zinc might contribute to the pathogenesis of acute diarrhea and the degree of success achieved in diarrhea control and treatment by zinc supplementation. Animal and in vitro studies have continued to fascinate the scientific fraternity and form a solid basis for the potential use of zinc supplementation against diarrhea. However, emerging evidence in terms of controlled studies in humans beckons a more complete understanding of the mechanistic basis for zinc supplementation. Current evidence indicates that studies specifically addressing the variability in response to zinc supplementation need to be undertaken to better comprehend these mechanisms.