Osteoporosis is a serious health problem worldwide that is associated with an increased risk of fractures and mortality. Vascular calcification is a well-defined independent risk factor for cardiovascular disease (CVD) and mortality. Major advances in our understanding of the pathophysiology of osteoporosis and vascular calcification indicate that these two processes share common pathogenetic mechanisms. Multiple factors including proteins (such as bone morphogenetic proteins, receptor activator of nuclear factor κB ligand, osteoprotegerin, matrix Gla protein and cathepsins), parathyroid hormone, phosphate, oxidized lipids and vitamins D and K are implicated in both bone and vascular metabolism, illustrating the interaction of these two, seemingly unrelated, conditions. Many clinical studies have now confirmed the correlation between osteoporosis and vascular calcification as well as the increased risk of CVD in patients with osteoporosis. Here, we explore the proposed mechanistic similarities between osteoporosis and vascular calcification and present an overview of the clinical data that support the interaction between these conditions.