Cyclic vomiting syndrome is a disorder of unknown etiology that is characterized by its clinical pattern of rapid-fire, episodic (on-off) vomiting with interval wellness. The pattern is stereotypic within individuals and typified by a rapid onset during the night or early morning, rapid denouement, and associated symptoms of pallor, lethargy, anorexia, nausea, retching, vomiting, and abdominal pain. The vomiting appears to be triggered by a variety of physical and psychological stresses. The disorder usually begins in toddlers and resolves during adolescence. By definition, cyclic vomiting syndrome is an idiopathic disorder that requires exclusionary laboratory testing. Not only can it be mimicked by many specific disorders, eg, surgical, neurologic, endocrine, metabolic, renal, but within idiopathic cyclic vomiting syndrome there may be specific subgroups that have different mechanisms. Treatment options are improving at present and serotonergic agents have the most promise. Although the pathogenesis is unknown, there are now several tenable mechanisms including migraine, metabolic, neuroendocrine, and gastrointestinal. Cyclic vomiting syndrome may be a useful model for the study of emesis.