Osteoporosis and cardiovascular disease were long viewed as independent of each other. However, numerous epidemiological studies, which are discussed in the first part of this review, have provided incontrovertible evidence of a link. Thus, the risk of coronary artery disease and stroke is higher in patients with a history of osteoporotic fracture or low bone mineral density than in non-osteoporotic patients. In the other direction, patients with cardiovascular disease are at higher risk for bone loss and osteoporotic fracture. The link between osteoporosis and cardiovascular disease is due in part to shared conventional risk factors such as estrogen deprivation in women, smoking, low physical activity, and diabetes. In addition, atheroma plaque calcification involves cytokines and growth factors that also play a role in bone turnover, including proinflammatory cytokines (IL-6 and TNFα), osteoprotegerin, sclerostin, matrix GLA protein, and FGF-23. Several recent studies have provided support for these pathophysiological hypotheses. Thus, elevation of osteoprotegerin, sclerostin, or FGF-23 levels may explain and predict the occurrence of both osteoporotic fractures and cardiovascular events. The association between osteoporosis and cardiovascular disease found in most epidemiological and pathophysiological studies suggests a need for evaluating potential benefits from routine bone absorptiometry and osteoporotic fracture detection in patients with cardiovascular disease and from exercise testing and arterial Doppler imaging in patients with osteoporosis.