Phosphate is an essential ion for mineralization of bone. Hypophosphatemia leads to rickets and osteomalacia whereas hyperphosphatemia promotes ectopic calcification in soft tissues. FGF23 is a polypeptide hormone secreted by bone that regulates serum phosphate concentration. It acts on kidney to decrease phosphate reabsorption, and 1,25-dihydroxy vitamin D secretion which in turn reduces phosphorus absorption by the gut. Its action on the renal tubule appears to require PTH activity. Secretion of FGF23 in humans is regulated by several factors including dietary phosphorus, 1,25-dihydroxy vitamin D, and iron status. However, the phosphate-sensing pathway through which dietary phosphorus regulation occurs remains unknown. The hormone contains a proteolytic cleavage site and both intact bioactive FGF23 and inactive N- and C-terminal fragments are present in serum. Clinical assays are available for intact FGF23 and for C-terminal FGF23 which measures intact hormone plus C-terminal fragments. The C-terminal fragment may act as an antagonist to the FGF23 receptor. The FG23 receptor is a complex comprising FGFR1 and Klotho a co-receptor produced and secreted by the kidney. Diseases of the FGF23/1,25-dihydroxy vitamin D/PTH endocrine axis are caused by both rare monogenetic and common acquired diseases. The commonest genetic disease with increased secretion of FGF23 is X-linked hypophosphatemia (XLH) causing rickets and osteomalacia whereas hyperphosphatemic familial tumoral calcinosis is due to decreased FGF23 activity. The commonest acquired disease of over secretion of FGF23 is chronic renal failure. Treatment with monoclonal antibody to FGF23 in XLH adult patients aimed at decreasing FGF23 activity, increases serum phosphate and 1,25-dihydroxy vitamin D without adversely affecting other aspects of mineral homeostasis. Such treatment may prove useful in other genetic and acquired diseases of excess FGF23 secretion.