Calcific aortic stenosis (CAS) is currently recognized as the third most frequent cardiovascular disorder in persons aged above 60 years, after atherosclerotic disease and hypertension, and together with its precursor aortic sclerosis it has been found in more than 30% of elderly individuals. CAS is an active multifactorial process characterized by a progressive fibro-calcific remodeling and thickening of the AV leaflets caused by hemodynamic flow factors, genetic factors, lipoprotein deposition, oxidation, chronic inflammation, immunomodulators, and finally osteoblastic transformation of cardiac. Herein a comprehensive state-of-the-art paper is presented regarding the underlying pathophysiological mechanisms of CAS and the potential preventive strategies as an alternative to surgical and interventional treatment.