Potassium and magnesium balance are frequently altered by common pathological conditions. Isolated disturbances of potassium balance do not produce secondary abnormalities in magnesium homeostasis. In contrast, primary disturbances in magnesium balance, particularly magnesium depletion, produce secondary potassium depletion. This appears to result from an inability of the cell to maintain the normally high intracellular concentration of potassium, perhaps as a result of an increase in membrane permeability to potassium and/or inhibition of Na+-K-ATPase. As a result, the cells lose potassium, which is excreted in the urine. Repletion of cell potassium requires correction of the magnesium deficit. Are such magnesium dependent alterations in potassium balance of any clinical significance? Within the context of electrolyte disturbances, magnesium replacement is often necessary before hypokalemia and potassium depletion can be satisfactorily corrected with potassium supplements. The hyponatremia often seen with chronic diuretic usage may also be related to depleted intracellular potassium stores. In a small group of patients with chronic congestive heart failure, magnesium replacement alone was sufficient to correct this hyponatremia. Finally, magnesium and potassium depletion may play an important role in the development of cardiac arrhythmias in certain select groups of patients, such as those with overt ischemic heart disease. The frequency of magnesium depletion in some clinical disease states warrants renewed interest in the relationship between magnesium and potassium homeostasis.