Patients with unexplained chest pain remain a difficult and perplexing challenge for the gastroenterologist. Despite exclusion of a cardiac origin many patients remain disabled by pain. In these, a diligent search for an esophageal cause-gastroesophageal reflux disease, motility abnormalities, or esophageal hypersensitivity using all available diagnostic (therapeutic) tools-results in a positive outcome. Appropriate use of a diagnostic trial of therapy, ambulatory pH monitoring and/or esophageal manometry, necessitates understanding of the respective benefits. The recent literature examines the value of a short course of high-dose proton pump inhibitors in establishing a diagnosis of gastroesophageal reflux disease-associated chest pain, the use of tricyclic antidepressants, and behavioral therapy in the management of these difficult patients with nonreflux, noncardiac chest pain.