A growing body of experimental, epidemiologic and physiologic evidence testifies to the hazards of hypokalemia and other electrolyte disorders that can complicate the chronic use of diuretic drugs in patients with cardiovascular disease. This study reviews the complex renal and extrarenal mechanisms that regulate potassium balance in normal persons with special attention to the role of stress-related hormones. Disturbances of potassium balance are common in patients taking diuretics; indeed, the potential number of people in this country at risk of diuretic-related hypokalemia approaches 9 million. The magnitude of this problem is of particular concern, because of the compelling data that link hypokalemia in such patients to electrical instability of the heart and to a fatal outcome after an acute cardiac injury. Therefore, aggressive correction of hypokalemia is warranted in patients with cardiovascular disorders.