Although amino-terminal pro-B-type natriuretic peptides (NT-proBNP) are useful for the diagnosis or exclusion of heart failure (HF), this marker may identify a wide range of disease processes other than HF. Indeed, elevation of NT-proBNP may occur in a number of heart diseases (including heart muscle disease, valve disease, rhythm abnormalities, pulmonary hypertension, and cytotoxic injury to the heart) and in disease processes other than primary cardiac illnesses, including gram-negative sepsis. Importantly, although NT-proBNP may increase in settings other than HF, the presence and severity of such NT-proBNP release is often significantly associated with risk for adverse outcome. Accordingly, elevation of NT-proBNP in the context of non-HF situations should not be regarded as a "false-positive" finding, and elevated NT-proBNP values should not be discarded without consideration of the serious adverse outcomes associated with the elevation. Future studies will be necessary to further understand the utility of NT-proBNP testing in states other than cardiovascular disease.