Calcific aortic stenosis, with a prevalence of 3-9%, is the most frequent heart valve disease and the main cause for valve replacement in patients over 60 years of age. Once thought to be caused by a passive calcium precipitate within the aortic valve leaflets, there is now increasing evidence that development and progression of calcific aortic valve disease may be triggered by underlying genetic and cardiovascular risk factors, and is regulated by an active cellular process involving inflammatory pathways. Targeted drug therapy to prevent the progression of calcific aortic valve disease should ideally be based on the knowledge of risk factors and the molecular pathogenesis of the disease. Conflicting data exists on the potency of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (i.e. statins) to influence both risk factors and inflammatory pathways by lowering lipid levels and exerting anti-inflammatory properties, respectively. In this review, various aspects of the molecular pathogenesis of calcific aortic stenosis will be summarized and connected with recent experimental and clinical studies that address the potential benefit of the targeted drug therapy by statins in order to prevent the progression of the disease.