The role of potassium in the progression of cardiovascular disease is complex and controversial. Animal and human data suggest that increases in dietary potassium, decreases in urinary potassium loss, or increases in serum potassium levels through other mechanisms have benefits in several disease states. These include the treatment of hypertension, stroke prevention, arrhythmia prevention, and treatment of congestive heart failure. Recently, the discovery that aldosterone antagonists not only decrease sodium reabsorption and decrease potassium secretion in the nephron, but also decrease pathological injury of such nonepithelial tissues as the myocardium and endothelium, has generated great controversy regarding the actual mechanisms of benefit of these agents. We review the available data and draw conclusions about the relative benefits of modulating potassium balance versus nonrenal effects of aldosterone blockade in patients with cardiovascular disease.