Diarrheal disease is a worldwide problem that still causes significant morbidity and mortality among children. Currently, oral rehydration solution (ORS) is the standard of care for acute diarrhea in pediatric patients. Although effective in reducing mortality, ORS does not alleviate diarrheal symptoms, thus reducing caregiver compliance and therapeutic efficacy. This article will briefly review the current problem of pediatric diarrhea and the shortcomings of current therapies; however, the focus of this review is to examine the intestinal calcium-sensing receptor (CaSR). The author summarizes the evidence suggesting that targeting the CaSR will enable clinicians to address all four major pathophysiological mechanisms of diarrheal disease, and substantiates the need for future research regarding this therapy.