Across the entire spectrum of ischemic heart disease, amino-terminal pro-B-type natriuretic peptides (NT-proBNP) are a strong and independent prognostic indicator, representing a particularly strong predictor of heart failure or death. This risk is independent of all other variables, including renal function or troponin, and is proportional to the magnitude of NT-proBNP release, with higher risk observed among those with a more marked elevation of the marker. Although prospective studies on the effect of NT-proBNP measurement in guiding therapy in ischemic heart disease are lacking, among patients presenting with acute coronary syndromes, it is recommended to measure NT-proBNP on (or near) the time of admission. An elevated initial NT-proBNP concentration should prompt consideration of an early invasive management approach. Consideration should be given to repeating the NT-proBNP measurement after 24-72 hours and again at 3-6 months because these follow-up measurements provide more long-term prognostic information than single measures at presentation. In acute ischemic heart disease, an NT-proBNP value >250 ng/L is associated with an adverse prognosis. In patients with stable coronary artery disease, measurement may be performed for prognostication purposes at 6- to 18-month intervals. In the case of clinical suspicion of disease progression, a new sample may be warranted.