Phosphate diabetes is defined as inadequate tubular reabsorption. Hypophosphatemia is responsible for most of the clinical manifestations, which vary with the age of the patient and the severity of the phosphate wasting. Vitamin D-resistant rickets in children or osteomalacia in adults, osteoporosis, bone pain including spinal pain, and pain in the joints and periarticular areas are the main manifestations. Several factors are known to affect tubular phosphate reabsorption via the sodium/phosphate cotransporters located on the tubular cell membranes. Factors that decrease phosphate reabsorption include a high intake of dietary phosphate, acidosis, parathyroid hormone (PTH), PTH-related peptide (PTHrp), glucocorticoid therapy, calcitonin, and vitamin D. On the other hand, a low-phosphate diet, alkalosis, growth hormone, insulin, IGF-1, and thyroid hormones increase tubular phosphate reabsorption. Physiological concepts about tubular phosphate reabsorption have been radically changed by the recent identification of phosphaturic factors called phosphatonins. The most extensively studied phosphatonin to date is fibroblast growth factor 23 (FGF23), which was first identified in patients with tumor-induced osteomalacia and shown to be secreted by the neoplastic cells. The FGF23 has also been implicated in autosomal dominant hypophosphatemic rickets, in which a gene mutation results in production of abnormal FGF23 that resists hydrolysis. In healthy individuals, FGF23 contributes to regulate phosphate reabsorption via Na/Pi cotransporters. Other phosphatonins may exist, such as matrix extracellular phosphoglycoprotein (MEPE) and secreted frizzled-related protein 4 (SFRP4), whose role remains to be defined. The part played by these proteins in idiopathic renal phosphate wasting in adults needs to be investigated.