When vomiting is not related to preventing the entry of physically or chemically unsuitable substances into the absorbing gut, it may be regarded as pathologic. The commonest causes of chronic vomiting are structural lesions affecting the mucosa of the upper gastrointestinal tract (often with luminal obstruction) and psychogenic disorders. Diseases affecting extrinsic and intrinsic neural control of gut motility and visceral smooth muscle may also cause unexplained vomiting. A stratified management approach to patients with vomiting is suggested. The first assessment is aimed at exclusion of mucosal lesions of the upper gut and systemic or psychiatric disease that may affect it. Second is a therapeutic trial, usually with a prokinetic agent. The final phase, reserved for recalcitrant undiagnosed patients, is evaluation at special centers with gastric emptying studies, gastrointestinal manometry, other electrophysiologic studies, and, in a few patients, laparotomy with examination of full-thickness biopsy specimens of the small intestine.