Serum parathyroid hormone (PTH) levels start to rise once the glomerular filtration rate falls below 60 ml/min with secondary hyperparathyroidism (2HPTH), becoming an almost universal complication in dialysis dependent chronic kidney disease (CKD). A better knowledge of the biological functions of the calcium-sensing receptor (CaSR) and the vitamin D receptor (VDR), and especially the recent discovery of fibroblast growth factor 23 (FGF-23) and the elucidation of its function as a phosphaturic and 1,25(OH)2VitD counterregulatory hormone have provided a new conceptual framework for the understanding of the pathogenesis of 2HPTH.