The improved treatment of acute diarrhea in children during the past 35 years has reduced its morbidity and mortality substantially. However, better therapy still is required. This article reviews the role of oral rehydration solution in the treatment of acute diarrhea with particular attention to recent efforts to develop improved oral rehydration solution formulations. One promising approach is the administration of Zinc (Zn). Based on its beneficial effects in infections, including pneumonia, Zn has been shown to be effective in the treatment of acute diarrhea in several randomized controlled trials including subsequent meta-analyses. Thus, an emerging body of clinical data indicates that Zn can be useful for treating acute diarrhea. However, only limited information is known about the mechanism(s) by which Zn reduces diarrhea. Recent studies have indicated that Zn acts as a K channel blocker of adenosine 3',5'-cyclic monophosphate-mediated chlorine secretion, but may not affect either Ca2+- or guanosine 3',5'-cyclic monophosphate-mediated chlorine secretion. These data provide a strong rationale for further trials testing its efficacy in specific clinical settings and for more detailed physiologic studies examining how Zn exerts its antidiarrheal effect.