Although hyponatremia is a common, usually mild, and relatively asymptomatic disorder of electrolytes, acute severe hyponatremia can cause substantial morbidity and mortality, particularly in patients with concomitant disease. In addition, overly rapid correction of chronic hyponatremia can cause severe neurologic deficits and death, and optimal treatment strategies for such cases are not established. An expert panel assessed the potential contributions of aquaretic nonpeptide small-molecule arginine vasopressin receptor (AVPR) antagonists to hyponatremia therapies. This review presents their conclusions, including identification of appropriate treatment populations and possible future indications for aquaretic AVPR antagonists.