Treatment of noncardiac chest pain is often difficult because of the heterogeneous nature of the disorder. This condition can stem from gastroesophageal reflux, visceral hyperalgesia, esophageal motility disorders, psychiatric dysfunction, abnormal biomechanical properties of the esophageal wall, sustained esophageal contractions, abnormal cerebral processing of visceral stimulation, or disrupted autonomic activity. For a treatment to be successful, diagnosis of the underlying cause is essential. This article examines three decades of studies from around the world. It concludes that new research into additional mechanisms involved in visceral pain appears promising; but that future studies using improved selective adenosine receptor antagonists and other therapeutic interventions are needed.