The kidney is a key player in phosphate balance. Inappropriate renal phosphate transport may alter serum phosphate concentration and bone mineralization, and increase the risk of renal lithiasis or soft tissue calcifications. The recent identification of fibroblast growth factor 23 (FGF23) as a hormone regulating phosphate and calcitriol metabolism and of klotho has changed the understanding of phosphate homeostasis; and a bone-kidney axis has emerged. In this review, we present recent findings regarding the consequences of mutations affecting several human genes encoding renal phosphate transporters or proteins regulating phosphate transport activity. We also describe the role played by the FGF23-klotho axis in phosphate homeostasis and its involvement in the pathophysiology of phosphate disturbances in chronic kidney disease.