A constant extracellular Ca2+ concentration is required for numerous physiological functions at tissue and cellular levels. This suggests that minor changes in Ca2+ will be corrected by appropriate homeostatic systems. The system regulating Ca2+ homeostasis involves several organs and hormones. The former are mainly the kidneys, skeleton, intestine and the parathyroid glands. The latter comprise, amongst others, the parathyroid hormone, vitamin D and calcitonin. Progress has recently been made in the identification and characterisation of Ca2+ transport proteins CaT1 and ECaC and this has provided new insights into the molecular mechanisms of Ca2+ transport in cells. The G-protein coupled calcium-sensing receptor, responsible for the exquisite ability of the parathyroid gland to respond to small changes in serum Ca2+ concentration was discovered about a decade ago. Research has focussed on the molecular mechanisms determining the serum levels of 1,25(OH)2D3, and on the transcriptional activity of the vitamin D receptor. The aim of recent work has been to elucidate the mechanisms and the intracellular signalling pathways by which parathyroid hormone, vitamin D and calcitonin affect Ca2+ homeostasis. This article summarises recent advances in the understanding and the molecular basis of physiological Ca2+ homeostasis.