Secondary hyperparathyroidism (SHPT) is a classical feature of chronic kidney disease (CKD). Commonly, hypocalcemia, hyperphosphatemia, and vitamin D deficiency are involved into the pathogenesis of SHPT. Parathyroid (PT) glands are characterized by a low turnover and rarely undergo mitoses. However, in the presence of low calcium, high phosphorus, vitamin D deficiency, and uremia, PT cells leave quiescence. In the last decade, both new molecular and cellular mechanisms have been investigated in the pathophysiology of SHPT, between them the emerging role of the PT vitamin D receptor and calcium-sensing receptor. Furthermore, recent studies indicate that the fibroblast growth factor-23 may play a central role in the regulation of phosphate-vitamin D metabolism in CKD. Certainly, in the next future, these new insights into the pathogenesis of SHPT will give the possibility to improve the treatment of this condition in the CKD population.