With the aging of the general population in industrialized nations, calcific aortic stenosis (CAS) is becoming an increasingly important medical problem. The etiology is for the most part, dependent on the age at presentation; the two predominant causes in the western world are calcific aortic valve disease arising in a tricuspid aortic valve and bicuspid aortic valve (BAV). CAS is a progressive disease, exhibiting a spectrum of pathologic findings, ranging from valvular sclerosis to severe nodular calcification. Aortic valve replacement is the recommended treatment for severe disease but tissue valves may also calcify over time. Various atherosclerotic risk factors have been linked to aortic stenosis and there are mechanistic similarities between atherosclerosis and CAS. The precise pathologic mechanisms underlying aortic stenosis are poorly understood.