Hypercalciuria is the single most important risk factor for stone disease and renal phosphate excretion is a recognized cause of absorptive hypercalciuria. The recent identification of "phosphatonins" that increase renal phosphate excretion has raised the possibility that these factors might be responsible for the phosphaturia seen in some patients with absorptive hypercalciuria. It is important to recognize that both parathyroid hormone and phosphatonins are phosphaturic, but they have opposite effects on 1,25(OH) 2D3 regulation. Serum concentrations of fibroblast growth factor-23, one of the phosphatonins, have been shown to be increased in some stone formers suggesting a pathogenic role. Future studies are needed to define the exact role of phosphatonins in nephrolithiasis.