The interrelationships of magnesium (Mg) and potassium (K) homeostasis are reviewed. Evidence from clinical and experimental studies including whole animal and cell culture experiments indicate that (1) homeostasis of Mg and K are closely related in the whole organism, (2) deficiencies of Mg and K frequently co-exist with gastrointestinal and especially renal losses from diuretic and nephrotoxic drug treatment being mainly responsible, and (3) Mg is required for maintenance of normal cellular K. Evidence from many laboratories indicate that Mg has direct effects at a cellular level on K transport. These include effects on Na-K-ATPase, Na-K-Cl cotransport, K channels, charge screening and permeability effects on membranes. New data on positive correlations between Mg and K in cardiac tissue, skeletal muscle and lymphocytes from patients undergoing cardiopulmonary bypass are presented. Interrelationships in Mg and K in cardiac tissue have probably the greatest clinical significance in terms of arrhythmias, digoxin toxicity, and myocardial infarction. Future studies will be aimed at elucidating mechanisms of Mg-K interrelationships at a cellular level using new techniques with the ability to detect concentrations and modulations of free intracellular Mg.