Heart failure is characterized by sodium and fluid retention, sympathetic overactivity, parasympathetic withdrawal, vasoconstrictor activation and cytokine elevation. Current treatment for acute heart failure consists of vasodilators, diuretics and inotropes. Nesiritide (human B-type natriuretic peptide) is a promising new class of drugs that has been given to almost 1,000 patients in numerous clinical investigations. The clinical development of nesiritide included dosing studies (utilizing repetitive boluses, continuous infusions, or a combination of bolus plus infusion), pivotal efficacy trials, and comparative safety studies, which have repeatedly demonstrated that intravenous nesiritide decreases pulmonary capillary wedge pressure, systemic vascular resistance, mean right atrial pressure and pulmonary artery pressure, while increasing cardiac index and stroke volume. Improvement in both clinical assessment and signs and symptoms of heart failure has been reported by patient and physician alike. Plasma levels of neurohormones and endothelin-1 are significantly reduced with nesiritide treatment. Compared with dobutamine, nesiritide is not proarrhythmic and does not affect heart rate. In comparison with intravenous nitroglycerin in the treatment of decompensated heart failure, nesiritide improves hemodynamics and symptomatology (dyspnea) faster and more effectively than nitroglycerin. Fewer patients receiving nesiritide reported any adverse event. Incidence of hypotension was comparable, but more intravenous nitroglycerin patients developed headache and abdominal pain. Current research supports an important role for the use of nesiritide in the treatment of decompensated heart failure.