Aortic stenosis is the most prevalent valve pathology and calcific aortic valve disease (CAVD) is its most frequent etiology in developed countries. There is extensive evidence that CAVD represents an active disease process similar to that of atherosclerosis with similar classical cardiovascular risk factors and pathological mechanisms. Given that in the vast majority of situations the only treatment available is valve replacement there is a need to develop pharmacological therapies that retard the disease progression. Lipid-lowering therapies have been the focus of research, however, so far with negative results. Future studies, including animal models, shall provide an opportunity to further evaluate the disease mechanisms of CAVD and to discover potential disease biomarkers and pharmacological interventions that can reduce the need for valve replacement.