Chest pain is the most common clinical presentation of acute ischemic heart disease, but only one third of these patients are ultimately found to have an acute coronary syndrome. Initial assessment of the patient presenting with chest pain includes a careful history, physical examination, an initial electrocardiogram (ECG) and measurement of biochemical markers of myocardial injury. The natriuretic peptide system is activated in a broad spectrum of cardiovascular diseases, including acute coronary syndromes and stable coronary disease. A strong relation between plasma levels of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) obtained in the subacute phase, and long-term, all-cause mortality, as well as the rate of re-admissions for heart failure after myocardial infarction, has been documented. Persistently elevated NT-proBNP levels during the first 72 hours following admission for an acute coronary syndrome have recently been associated with the presence of refractory ischemia and high risk of short-term recurrent ischemic events. Patients with signs of exercise-induced ischemia by dobutamine stress echocardiography have been reported to have higher baseline BNP values. Moreover, BNP and NT-proBNP levels are increased acutely in proportion to the magnitude of the inducible perfusion defect observed during stress testing, suggesting that BNP and NT-proBNP are markers of acute ischemia. Recently, a relationship between circulating levels of BNP and NT-proBNP and long-term all cause mortality in patients with stable coronary artery disease has been documented.