Approximately 30% of coronary angiograms performed in this country are negative for significant coronary artery disease. These patients are classified as having noncardiac or unexplained chest pain (UCP). Despite the good overall prognosis, this condition has significant morbidity and costs. The pathophysiology of this condition is likely caused by overlapping cardiac, esophageal, and psychiatric abnormalities with visceral hyperalgesia playing a central role. Gastroenterologists are often consulted in the evaluation of these patients because esophageal disorders are among the most common conditions associated with UCP. However, clinical symptoms are unreliable in differentiating between esophageal and cardiac causes of UCP. Gastroesophageal reflux disease, not esophageal motility disorders, is the most common esophageal disorder present in patients with UCP. The most useful diagnostic test in the evaluation of UCP is 24-h pH monitoring. An initial empiric trial of high-dose acid suppression is the most cost-effective intervention in the management of these patients. A clinical algorithm is suggested for the evaluation and treatment of UCP.