Cyclic vomiting syndrome (CVS) is a chronic, recurrent disorder of unknown etiology characterized by episodes of nausea and vomiting lasting hours or days and separated by symptom-free intervals of weeks to months. Although several different therapeutic regimens have been suggested for CVS, there remains no standard, effective regimen. In many cases, management of vomiting episodes includes the use of potent sedatives that induce prolonged durations of sedation and sleep. Dexmedetomidine is an alpha(2) adrenergic agonist with an increased specificity for the alpha(2) versus the alpha(1) receptor when compared with clonidine. Several physiologic effects have been demonstrated with dexmedetomidine including sedation, anxiolysis, analgesia, and blunting of the sympathetic nervous system. We report, for the first time, successful use of dexmedetomidine to treat CVS in 3 pediatric-aged patients. Potential mechanisms for its efficacy and future potential as a therapeutic agent for CVS are discussed.