Acute gastroenteritis (AGE) in the pediatric population remains a significant cause of pediatric patient morbidity and mortality. For these patients, oral rehydration therapy is an intervention that should be initiated with the first signs and symptoms of AGE. Oral rehydration therapy should be based on the degree of clinical dehydration. Clinical findings, such as those used in the clinical dehydration score, should be utilized as a means to standardize the dehydration assessment. Recent evidence supports the use of ondansetron, both orally and intravenously, to facilitate oral rehydration when vomiting is a concern. Consideration should be given to a trial of ondansetron therapy in the management of children with AGE to potentially avoid intravenous rehydration and hospital admission.