One third to one half of cases of dyspepsia remain unexplained. The cause of nonulcer dyspepsia is unknown, but aerophagia, esophageal dysfunction, pyloroduodenal dysmotility and the irritable bowel syndrome may be important factors in some patients. The symptoms are often affected by diet and emotion. History-taking and endoscopy are the most discriminating diagnostic tests. Unexplained dyspepsia tends to be a lifelong disease with few, if any, sequelae. Nevertheless, reassurance and treatment with a placebo, such as an antacid or simethicone, provide effective and safe relief for many patients.