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Review of research directions in the etiology, evaluation, and treatment of patients with noncardiac chest pain. The author proposes a combined practical approach to noncardiac chest pain that incorporates these findings, which is useful in a clinical practice setting.Several major schools of thought have emerged in the etiology of noncardiac chest pain: acid reflux, motor disorder, altered pain threshold/hypersensitivity, and association with psychiatric dysfunction. There is significant overlap among these. Occult gastroesophageal reflux disease (GERD) is more common than motor disorders and is found in 30% to 40% of these patients; a subset has hypersensitivity, with a normal pH profile. Esophageal motility testing and endoscopy have a more limited role than 24-hour pH testing. Impedance planimetry and balloon sensory provocative testing remain research tools. Provocative testing with hydrochloric acid or edrophonium is less helpful than pH monitoring. Gastroesophageal reflux disease–induced chest pain requires high-dose long-term proton pump inhibitors (PPIs): at least 4 to 8 weeks. Psychotropics are superior to placebo, both in patients with and without psychiatric dysfunction.The author found combined PPIs and psychotropics helpful in patients with esophageal hypersensitivity and GERD, although supporting data is scant.A brief 1-week high-dose PPI challenge, i.e., omeprazole test, may be cost-effective in a primary care setting. However, this approach may not be useful in a referral setting, where pH data and diary assessment of associated symptoms provide useful management help. A behavioral model approach, with early emphasis on patient education, integrated with physiologic data helps the most.