Acute decompensated heart failure (ADHF) represents the most common discharge diagnosis in patients over age 65, and has an exceptionally high mortality and readmission risk. ADHF is characterized by abnormal hemodynamics, including increase in pulmonary capillary wedge pressure and peripheral vasoconstriction, although cardiac index may be reduced, normal, or increased. Myocardial injury, which may be related to decreased coronary perfusion, activation of neurohormones, and/or renal dysfunction, may contribute to short-term and postdischarge cardiovascular events. Recent ADHF registries have provided valuable insights into the characteristics, treatment patterns, and clinical outcomes of these patients. Most patients with ADHF present with either normal systolic blood pressure or elevated blood pressures; hypotension is relatively uncommon. These patients have significant cardiovascular and noncardiovascular comorbidities that may contribute to the pathogenesis and/or adverse outcomes in ADHF. Therapies for ADHF have been targeted to improve symptoms and hemodynamics, as well as preserve or improve renal function, prevent myocardial damage, modulate neurohumoral and inflammatory activation, and manage other comorbidities that may cause and/or contribute to the progression of this syndrome. Concomitant therapies proven to provide long-term benefits in chronic heart failure are also essential. There remains an unmet need for therapeutic approaches for the early management of ADHF that may improve short- and long-term outcomes. Ongoing clinical trials are intended to provide data that will better define the benefits and risks of therapies for ADHF.