Most patients admitted with acute decompensated heart failure (ADHF) go through the emergency department as their initial point of care. New diagnostic tests hold the promise to improve the clinical accuracy of the emergency physicians’ diagnosis. Beyond that there is growing recognition that the treatment provided initially has an important impact on the subsequent inpatient course. Basic care for ADHF has involved oxygen as needed, diuretics, and, occasionally, topical or sublingual nitroglycerin. A substantial proportion of patients are treated with vasoactive agents including inotropes and vasodilators such as nitroglycerin and nesiritide. Unfortunately, inotropes have not been demonstrated to improve the outcome of heart failure and, in fact, may be deleterious. The newer agent, nesiritide, has the advantage of being a balanced vasodilator with favorable effects on diuresis, symptom relief, and neurohormones. Evidence from registries indicates that early initiation of nesiritide compared to delayed initiation leads to improved outcomes with shorter lengths of stay, shorter stays in the intensive care unit, and a lower mortality rate. This article reviews the initial management of ADHF, the role of early initiation of vasodilator therapy, and the pharmacoeconomics of nesiritide treatment.