Magnesium (Mg) is the second most abundant intracellular cation and is a cofactor in more than 300 enzymatic reactions involving energy metabolism and protein and nucleic acid synthesis. Ionized Mg is the physiologically active form of the element. Protein-bound and chelated Mg buffer the ionized pool. Approximately half the total Mg in the body is present intracellularly in soft tissue, and the other half is present in bone. Less than 1% of the total body Mg is present in blood. However, the majority of our clinical laboratory information comes from the determination of total Mg in serum. Currently, the clinical laboratory evaluation of Mg status is limited primarily to the total serum Mg concentration and a 24-hour urinary excretion. Instrumentation to determine ionized Mg in serum (ion-selective electrode) and in soft tissue (nuclear magnetic resonance spectroscopy) should be available in the near future. Magnesium may be a factor in the treatment of acute myocardial infarction and the rate of atherosclerosis. Chronic changes of Mg status, that may be latent, are poorly understood and require a better knowledge of ionized Mg metabolism.