Bone and teeth work as hard tissues to support several biological functions. Proper mineralization is necessary for these tissues. In contrast, ectopic calcification usually has deleterious effects on the function of the calcified tissues. Therefore, there should be mechanisms to prevent ectopic calcification. Vascular calcification is a complex process. Several enzymes, minerals, cytokines and cells are involved in the development of vascular calcification. For example, ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) encodes as enzyme that produces pyrophosphate, a potent inhibiter of calcification. Inactivating mutations in ENPP1 result in generalized arterial calcification of infancy (GACI) indicating that this enzyme activity is essential for the prevention of vascular calcification. In addition, it is well known that hyperphosphatemia is a risk factor for vascular calcification especially in patients with chronic kidney disease. Phosphate promotes the differentiation of vascular smooth muscle cells into osteoblast-like cells. In addition, hyperphosphatemia seems to enhance hydroxyapatite deposition in matrix vesicles. Serum phosphate level is mainly regulated by actions of parathyroid hormone and fibroblast growth factor 23 (FGF23). FGF23 is a phosphotropic hormone working through FGF receptor-Klotho complex. FGF23 knockout mice and Klotho mice with severely reduced expression of Klotho show similar phenotypes including hyperphosphatemia and vascular calcification. In human, impaired function of FGF23 causes hyperphosphatemic familial tumoral calcinosis (HFTC) characterized by hyperphosphatemia and ectopic calcification including vasculature. Three genes, FGF23, Klotho and GALNT3 have been identified to be responsible for HFTC. Mutations in these genes cause impaired function of FGF23 by different mechanisms. These results indicate that the maintenance of normal mineral metabolism is also necessary to prevent ectopic calcification.