Maintenance of normal blood levels of ionized calcium (Ca2+) plays an important role in the management of the critically ill patient. Therefore, Ca2+ should be collected properly and measured reliably. The sound analytical performance of today's Ca2+ analyzers using ion-selective electrode technology have made measurements accurate and precise. The introduction of this technology allows rapid and direct analysis in whole blood or serum, resulting in an enhanced reporting time. Since the amount of heparin in the syringe was shown to lower plasma ionized calcium concentration artifactually, samples for plasma Ca2+ determination should be anticoagulated with a measured quantity of heparin. Ancillary factors in Ca2+ determination include effects of changes in sample pH, and situations where abnormal concentrations of calcium ligands are present. Many clinical situations require Ca2+ rather than total calcium measurements. Liver transplantation, citrated blood transfusions, and neonatal hypocalcemia are examples of a few such circumstances where determination of Ca2+ may be more physiologically and clinically meaningful than total calcium.