Serum calcium and phosphate levels are tightly regulated by parathyroid hormone and vitamin D. Dysregulation of this homeostasis in patients with chronic kidney disease (CKD) contributes to the development of secondary hyperparathyroidism, which in turn induces cardiovascular disease as well as the further deterioration of the kidney function and bone abnormality, and eventually increases mortality and morbidity. Evidence for the relationship between circulating fibroblast growth factor 23 (FGF23) levels and the incidence of cardiovascular mortality has been accumulated. With the discovery of FGF23/klotho axis, we gained the understanding of adaptation and maladaptation of the phosphate handling in CKD patients. The research for the direct or indirect sequelae of increased serum FGF23 concentrations should be warranted.