Serum phosphate concentration value is controlled by the kidney, which adapts phosphate reabsorption in the proximal tubule to the needs of the body and regulates intestine absorption of phosphate and calcium through calcitriol synthesis. Fibroblast Growth Factor 23 (FGF23) is a hormone that controls sodium-phosphate transporter and 1-alpha 25(OH) vitamin D hydroxylase expression in the renal proximal tubule. FGF23 is synthesized by bone cells in response to an increase in serum phosphate or calcitriol concentrations. The binding of FGF23 to a FGF receptor requires a protein named Klotho that is expressed in the kidney in the distal but not in the proximal tubule. The mechanism by which FGF23 controls proximal tubule function remains to be established. The alteration of the FGF23-Klotho axis in animal models and various human disorders is associated with abnormal control of body phosphate content confirming the major role played by these protein in phosphate homeostasis. This review details FGF23 and Klotho functions in normal conditions and in genetics or acquired disorders.