Calcific aortic stenosis in the elderly is the number one cause of surgical valve replacement in the US and Europe. The incidence of calcific aortic stenosis is increasing as the general age of the population increases. For many years, rheumatic heart disease was the main cause of aortic valve disease. Over the last half century, however, there has been a change from a rheumatic etiology to a 'degenerative' mechanism because of the increase in access to health care in developed countries and the increasing age of the population in the US and Europe. For many years 'degenerative' aortic stenosis was thought to be caused by the passive accumulation of calcium on the surface of the aortic valve leaflet. Recent studies have demonstrated, however, that the etiology of aortic valve disease has a similar pathophysiology to that of vascular atherosclerosis, and that the treatment of this disease could be similar to that of chronic vascular atherosclerosis. This Review will discuss our current understanding of the pathophysiology, risk factors, cellular mechanisms, diagnosis and finally, future medical therapies for calcific aortic stenosis.