Dyspepsia, defined as chronic or recurrent upper abdominal pain or nausea, is a common occurrence. Dyspepsia without an ulcer (non-ulcer dyspepsia) is diagnosed in patients at least twice as often as peptic ulceration. Diseases that may present with similar symptoms include gastroesophageal reflux, biliary tract disease, chronic pancreatitis, and irritable bowel syndrome. A careful history and physical examination, supplemented by selected tests, usually lead to a correct diagnosis. The pathogenesis of non-ulcer dyspepsia remains unknown. Gastric acid secretion, duodenogastric reflux, psychological factors, environmental exposures, and heredity probably do not play a major role. Some patients may have motility disturbances, but whether these disturbances cause dyspepsia is unknown. Campylobacter pylori infection and associated gastritis are common in non-ulcer dyspepsia, but their etiologic role is controversial, as is the importance of chronic duodenitis. By recognizing the heterogeneity of patients who present with non-ulcer dyspepsia, more rational management may be possible. Although an empiric trial of antacids or H2 blockers has been recommended to treat dyspepsia, most controlled trials show that although these substances reduce severity of symptoms, they are no more effective than placebos in non-ulcer dyspepsia.