The therapeutic goals for patients hospitalized with acutely decompensated heart failure are to reverse acute hemodynamic abnormalities, relieve symptoms, and to initiate heart failure therapies which will decrease disease progression and improve long-term survival. Nesiritide (recombinant B-type natriuretic peptide) is the first in a new class of therapeutic agents for the treatment of heart failure and has been demonstrated to offer a unique combination of safety and efficacy. The use of nesiritide on top of standard care including diuretic therapy, has been proven to lead to meaningful clinical benefits in a broad range of acutely decompensated heart failure patients. Nesiritide is an attractive therapeutic option because of its more rapid and sustained hemodynamic profile, more favorable effects on neurohormonal suppression, with less adverse effects than alternative intravenous heart failure treatments such as nitroglycerine, nitroprusside, dobutamine, or milrinone. The use of nesiritide is the most effective initial treatment approach among currently available strategies to reverse acutely decompensated heart failure and to facilitate optimization of the heart failure medical regimen.