Osteoporosis and atherosclerosis are degenerative disorders of old age that often present together, but recently it has been suggested that the association between osteoporosis and cardio-vascular diseases is not just due to the aging process. The osteoprotegerin (OPG)/receptor activator of nuclear factor-kB (RANK)/RANK ligand (RANKL) system has been identified as a possible mediator of arterial calcification suggesting common links between osteoporosis and vascular diseases. Since the discovery of the OPG/RANK/RANKL system, much has been learned about its role in controlling skeletal biology; however, its role in the context of vascular biology is only beginning to be explored. It has been suggested that OPG might act as an autocrine/paracrine regulator of vascular calcification and might be useful as a serum marker of vascular disease. However, the exact role of OPG (or RANKL/RANK) in vascular calcification is still not completely understood. This review aims to report the recent findings on the relationship between osteoporosis and OPG/RANK/RANKL-mediated vascular disease.