Calcium is the most closely controlled substance in the blood. The biologic variation of total calcium is ~ 2% and of the biologically active free (ionized, ionic) calcium only 1%. (1-3) Thus, the monitoring of calcium in blood requires analytic procedures of high precision and accuracy. For patients with asymptomatic primary hyperparathyroidism, calcium monitoring involves the measurement of total calcium and free calcium. This review first considers the measurement of total calcium and then free calcium.