The demonstration of the calcium sensing receptor (CaSR) on the parathyroid glands cell membranes shed new light on the way serum calcium concentration stimulates or conversely suppresses PTH secretion. Abnormalities of the CaSR, either due to loss of function or gain of function, caused by inherited or acquired disorders, result in abnormalities in mineral metabolism. The latter at times might be associated with abnormalities in the CaSR in other tissues like the kidneys where the receptor regulates calcium excretion. The development of calcimimetic agents which lower the threshold of the CaSR enables treatment of conditions associated with hyperparathyroidism and future development of calcilytic agents will provide a tool in treating hypoparathyroidism. This review article will address our current understanding of the physiology, pathophysiology, diseases and clinical applications of the CaSR.