The clinical approach to the patient with unexplained chest pain is complex, as the history does not clearly separate cardiac from noncardiac etiologies. After a careful work-up has excluded coronary artery disease, a systematic search for an esophageal etiology is the next step. Gastroesophageal reflux disease (GERD) is most commonly associated with noncardiac chest pain and should be the first diagnosis pursued. A therapeutic trial of antisecretory therapy with proton-pump inhibitors is the most efficient initial approach to diagnosis and therapy of GERD-related chest pain and can easily be instituted by a cardiologist familiar with the optimal use of proton-pump inhibitors.