Fluid retention manifested by peripheral edema, fluid in the lungs, and ascites has been recognized as a sign of congestive heart failure from earliest times. In fact, in 1775, Withering,1 when describing the effects of the foxglove on patients with “dropsy,” believed that the major action of the drug was as a diuretic. Our present understanding of the pathophysiology of heart failure has evolved through the hemodynamic stage that focused on the heart as the primary cause with secondary effects on the kidney, where inotropic agents and diuretics were the mainstay of therapy to the neurohormonal stage. Here, activation of the sympathetic nervous system, the renin-angiotensin-aldosterone system, and vasopressin is recognized as increasing sodium and water retention, which elevates the intravascular volume and returns stroke volume and cardiac output to normal. Along with these temporary measures supporting the circulation come maladaptive consequences involving vasoconstriction, decreased renal blood flow, and sodium and water retention. Later effects are ventricular remodeling, loss of myocardial cells, and decreasing ventricular function. To counter these effects, β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, aldosterone, and vasopressin antagonists have become the modern optimal medical therapy for congestive heart failure.