The near constancy of extracellular calcium concentration is required for the numerous physiological functions of extra- and intracellular calcium. This implies that any change in extracellular calcium concentration must be detected in order to allow the appropriate correction by the homeostatic systems. The identification and cloning of a calcium-sensing receptor (CaR), which is expressed in the plasma membrane of parathyroid cells as well as many other cell types, has been a major advance in the understanding of the mechanisms involved in the control of extracellular calcium concentration. In addition, it demonstrated that extracellular calcium concentration itself is the first informative hormone-like messenger in this system. CaR belongs to the C subfamily of seven transmembrane-spanning G protein-coupled receptors. Several inherited disorders in extracellular calcium homeostasis are due to both activating or inactivating mutations in CaR gene, strengthening the essential role of CaR in the control of calcium metabolism.