This chapter talks about pathophysiology of chronic kidney disease mineral bone disorder (CKD-MBD). It discusses the pathogenetic factors such as fibroblast growth factor 23 (FGF23), Klotho, and hyperphosphatemia in the CKD-MBD. Depending on the relative contribution of the different pathogenic factors and their treatment, various pathologic patterns of bone remodeling are expressed in CKD and end-stage kidney disease (ESKD). Renal injury disturbs the complex physiology of bone and mineral metabolism, promotes vascular calcification, and compromises cardiac function. In addition, the effects of kidney disease on the skeleton contribute through the bone-cardiovascular axes to the major effect of kidney injury to stimulate cardiovascular disease and produce the high mortality rates associated with kidney disease. The pandemic of CKD and ESKD and the role of the CKD-MBD in the associated mortality, make the syndrome a major health issue for Americans and all developed societies.