Background Blocking the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors has improved cardiovascular morbidity and mortality rates. However, because of aldosterone “escape,” the effectiveness of this blockade decreases over time. Methods Various in vitro and in vivo studies were evaluated to determine the mechanisms by which aldosterone contributes to morbidity and mortality. Results Aldosterone has several deleterious properties. It causes a vasculopathy with both endothelial dysfunction and a reduction in fibrinolysis, leading to heart, brain, and kidney damage. Aldosterone causes myocardial hypertrophy and fibrosis, autonomic imbalance, and electrolyte abnormalities, contributing to myocardial dysfunction, arrhythmias, and sudden cardiac death. Studies have shown that all of these deleterious effects can, at least in part, be reversed by aldosterone receptor blockade. This may explain why adding an aldosterone blocker to standard heart failure therapy, including angiotensin-converting enzyme inhibitors, reduces morbidity and mortality rates by an additional 30% compared with standard therapy alone. Conclusions Eplerenone is a selective aldosterone blocker whose role in reducing morbidity and mortality rates in patients with cardiovascular disease is being investigated. (Am Heart J 2002;144:S2-7.)