The treatment of acute decompensated heart failure (ADHF) remains a therapeutic challenge. Nesiritide was approved by the FDA in 2001 for the treatment of patients with ADHF who have dyspnea at rest or with minimal exertion. Although widely adopted for the treatment of ADHF due to its ability to decrease ventricular filling pressures and to provide mild symptomatic benefit, recent analyses have suggested that nesiritide worsens renal function and increases mortality. Although some discount these analyses that demonstrate the potential dangers of nesiritide, others have stated that its use at the present time must be weighed against the possibility of worse outcomes. A large outcomes trial in patients with ADHF would help clarify the role of nesiritide.