This review outlines the chemical properties, pharmacology and clinical trials data which support the development of nesiritide (synthetic human B-type natriuretic peptide, or hBNP) as a therapeutic agent for patients with decompensated congestive heart failure. Nesiritide is a 32-amino acid peptide, structurally identical to endogenous hBNP. Clinical trials with single bolus, repeated boluses and sustained infusions of nesiritide have demonstrated prompt, significant and sustained reductions in pulmonary capillary wedge pressure and increases in cardiac output, consistent with a direct vasodilator effect. Nesiritide has a short half-life, approximately 18 min, which is not dependent upon renal function. It not associated with tachyphylaxis through 24 h of therapy. Nesiritide is not an inotrope, and its action is not dependent upon beta adrenergic receptors. The safety profile has been excellent; the major adverse effect is hypotension. The frequency of ventricular arrhythmia is not increased in patients treated with nesiritide. In our opinion, nesiritide has many attributes of an ideal first-line therapeutic agent for decompensated heart failure.