The observation that the intestinal Na⁺-glucose cotransporter remains intact in most diarrheal illnesses led to development of the life-saving, low-cost technology of oral rehydration salt (ORS) solutions. The primary therapeutic role of ORS solutions is in prevention and treatment of dehydration during management of acute gastroenteritis. Successful oral rehydration therapy involves early use of ORS with maintenance or timely resumption of regular feeding. Since the inception of the oral rehydration approach more than three decades ago, the widespread use of ORS solutions has revolutionized the management and outcomes of acute gastroenteritis in children and adults. The efficacy of the World Health Organization ORS solution and of commercial ORS formulations has been enhanced by reducing osmolarity. Newer formulations of ORS are under active investigation, with promise of added benefits, including promotion of intestinal healing. This article reviews fluid and electrolyte transport in the gastrointestinal tract, the pathophysiologic mechanisms of acute diarrhea, and the basis and formulation of current and newer ORS solutions. Guidelines for efficacious use of ORS in the management of acute gastroenteritis and short gut syndrome are also provided.