Considerable scientific progress in the pathogenesis of vascular calcification that has accrued in recent years is reviewed in this article. Factors regulating mesenchymal cell differentiation and their role in the neointimal calcification of atherosclerosis and the vascular media calcification observed in chronic kidney disease and diabetes are discussed, as is the role of bone regulatory proteins in bone mineralization and vascular calcification. This includes recent studies related to fetuin-A, and the discovery of a new circulating hormone involved in regulating phosphate homeostasis and sensing skeletal hydroxyapatite precipitation. Finally, the relationship between skeletal mineralization and vascular mineralization is discussed in terms of their links, especially through serum phosphate concentrations.