Calcific aortic stenosis is the most frequent heart valve disease and the main indication for valve replacement in western countries. For centuries attributed to a passive wear and tear process, it is now recognized that aortic stenosis is an active inflammatory and potentially modifiable pathology, with similarities to atherosclerosis. Statins were first-line candidates for slowing down progression of the disease, as established drugs in primary and secondary cardiovascular prevention. Despite promising animal experiments and nonrandomized human trials, the prospective randomized trials SEAS and SALTIRE did not confirm the expected benefit. We review SEAS and SALTIRE starting with the preceding studies and discuss basic science experiments covering the major known contributors to the pathophysiology of calcific aortic valve disease, to conclude with a hypothesis on the absent effect of statins, and suggestions for further research paths.