Bone is involved in the maintenance of phosphate and vitamin D homeostasis via its production and secretion of FGF23 and serves as a reservoir for the storage and release of calcium and phosphate into the circulation. Alterations in mineralization of extracellular matrix and the remodeling activities of the skeleton are coupled to the kidney conservation of phosphate and production of 1,25(OH)2D via the regulation of FGF23 production by osteocytes through yet-to-be defined locally derived factors. In addition, FGF23 production is regulated by 1,25(OH)2D in a feedback loop where FGF23 stimulate Cyp24 mediated degradation of 1,25(OH)2D that serves to protect the organism from the toxic effects of vitamin D excess. In this chapter, we will review the regulation and function of FGF23.