In patients presenting with acute dyspnea of any cause, elevation of amino-terminal pro-B-type natriuretic peptides (NT-proBNP) is powerfully prognostic for adverse outcomes, including death. Among those with acute destabilized heart failure (HF), an NT-proBNP cut point of approximately 5,000 ng/L is powerfully predictive of death by 76 days after presentation. For 1-year risk stratification, an NT-proBNP value of approximately 1,000 ng/L at presentation is optimal. Among those patients with elevated NT-proBNP levels, a posttreatment NT-proBNP value may be of even greater value than the presenting value. Although NT-proBNP is powerfully prognostic in patients with acute dyspnea with and without HF, the addition of clinical variables strengthens the ability to discriminate risk. In addition, multimarker approaches, including NT-proBNP, for the assessment of acute dyspnea or acute HF appear promising. Indeed, when combined with conventional markers, such as measures of renal dysfunction, anemia, myocardial injury, or inflammation, the predictive value of NT-proBNP is considerably strengthened. Given the strong value of NT-proBNP for risk assessment of the patient with acute dyspnea, a baseline measurement for all patients with dyspnea is recommended, with pretreatment and posttreatment measurement of NT-proBNP recommended for patients with an elevated value, especially those with HF.