During the past decades, our knowledge of renal phosphate handling has advanced dramatically. This advance is primarily due to the discovery of sodium-phosphate transport channels and their regulation in health and disease. The discovery of phosphatonins, initially in patients with tumor-induced osteomalacia, has not only allowed us to develop a better understanding of several rare diseases including vitamin D-resistant rickets, but also it has expanded our knowledge of the dynamic interaction between the bone and the kidney critical to bone mineralization. In this review, the author focuses on these new developments and their importance to our understanding of phosphate homeostasis in health and disease.