Levels of natriuretic peptides, including B-type natriuretic peptide and N-terminal prohormone brain natriuretic peptide, are strong independent predictors of prognosis in acute coronary syndrome (ACS). They are associated with short- and long-term mortality and with the risk of new-onset heart failure, above and beyond the conventional risk factors. Myocardial ischemia and ventricular wall stress are triggers for the release of natriuretic peptides, and although the latter are associated with the severity of the underlying coronary artery disease, they fail to predict recurrent nonfatal ACS. In conclusion, natriuretic peptide values may improve risk stratification in ACS when used in addition to troponin levels and other prognostic markers, but more data are needed to define their role in ACS therapy.