Humans are prone to sodium overload and potassium depletion. This electrolyte imbalance is important in the pathogenesis of cardiovascular disease and sudden cardiac death. Avoiding hypokalemia is beneficial in several cardiovascular disease states including acute myocardial infarction, heart failure, and hypertension. The evidence highlighting the importance of potassium homeostasis in cardiovascular disease and possible mechanisms explaining potassium's benefits are reviewed. Targets for serum potassium concentration are suggested.