Heart failure (HF) is one of the leading cardiovascular health problems in Europe and the United States. Acute decompensated HF remains a lethal diagnosis with a morbidity and mortality that often exceeds neoplastic or infective diseases. The incidence of HF continues to increase despite an intensive effort to increase education and delivery of healthcare to these affected patients. Yet, current guidelines in the United States do not address the management of acute decompensated HF, and focus predominantly on chronic stable systolic HF as well as patients with left ventricular dysfunction. Although the European Society of Cardiology has established some parameters for the management of acute HF, these guidelines are largely established by expert opinion, and are predominantly devoid of prospective randomized data in this cohort of patients. Current pharmacotherapies for acute decompensated HF include diuretics, neurohormonal antagonists, vasodilators, and inotropes. Regrettably, all of these drugs have their limitations in acute HF. Neurohormonal antagonists reduce morbidity and mortality, but may be inadequate to achieve and maintain the necessary hemodynamic relief required in advanced HF; while, bolus diuretics, a mainstay of initial symptomatic relief, may be maladaptive and up-regulate adverse neurohormonal regulatory mechanisms longterm with no positive impact on longterm mortality. Today, for those advanced HF patients who remain symptomatic despite optimal conventional therapy, limited treatments exist; but as newer therapies evolve, the options will expand to include more than palliative care, heart transplant and ventricular assist devices for these patients.