Non-cardiac chest pain or NCCP is defined as recurrent angina-like substernal chest pain of non-cardiac origin. Approximately 30% of coronary angiograms performed in USA are negative for significant coronary artery disease. These patients are classified as having non-cardiac or unexplained chest pain (NCCP/ UCP). Despite the good overall prognosis, this condition has significant morbidity and costs. Overlapping cardiac, esophageal, and psychiatric abnormalities with visceral hyperalgesia playing a central role likely cause the pathophysiology of this condition. Gastroenterologists are often consulted in the evaluation of these patients because esophageal disorders are among the most common conditions associated with NCCP. However, clinical symptoms are unreliable in differentiating between esophageal and cardiac causes of NCCP. Gastroesophageal reflux disease (GERD) is the most common esophageal disorder present in patients with NCCP. The most useful diagnostic test in the evaluation of NCCP is 24-hour pH monitoring. An initial empiric trial of high dose acid suppression is the most cost-effective intervention in the management of these patients.