Patients with unexplained or noncardiac chest pain continue to present a difficult challenge to the gastroenterologist. Cardiac disease must be ruled out first as the history will not distinguish between coronary artery disease and other causes of substernal chest pain. A systematic approach to evaluation should include reassurance that the heart is normal and attempts to confirm an esophageal etiology. Gastroesophageal reflux disease is the most common esophageal abnormality associated with unexplained chest pain and may be identified by an aggressive trial of anti-reflux therapy or an abnormal prolonged ambulatory pH monitoring study. Endoscopy is almost always normal and of less use in this population than in those with heartburn as the presenting symptom. Judicious use of manometry with provocative testing to evaluate for esophageal motility abnormalities or esophageal sensitivity allows for optimal evaluation of those who do not have gastroesophageal reflux disease. This article reviews the clinical presentation, differential diagnosis, and approach to evaluation and therapy of this complex group of patients.