Degenerative aortic valve stenosis is the leading cause of heart valve disease in elderly resulting in significant morbidity and mortality. Although aortic stenosis has been recognized as a complex inflammatory and well-regulated process, its exact pathomechanisms are still largely unknown. Assessment by Echocardiography, Electron Beam Computed Tomography and Multislice Computed Tomography is useful for monitoring of disease progression. However, better knowledge of main determinants is essential to enable both prediction and prevention of the disease. It has been suggested that the process of heart valve degeneration is associated with the risk factors of atherosclerosis and shares many histological and molecular characteristics. Morphologic, cellular and sub-cellular examinations of degenerative aortic valves revealed endothelial derangement, inflammatory infiltrates of macrophages, T-lymphocytes and foam cells, non-physiologic lipid / lipoprotein / protein deposits, as well as dramatically altered extra-cellular matrix composition and expression profiles of checkpoint- and ”tissue remodeling“-genes. Metabolic disorder - Diabetes mellitus - is considered to predispose to degenerative valve disease and is associated with faster degeneration of bioprosthetic valves. Oxidative stress is implicated in progressive chronic degenerative processes secondary to diabetes. Moreover, diabetic patients are a high-risk group for infectious disorders. Increased prevalence of infectious endocarditis in patients with type 2 Diabetes mellitus contributes considerably to both acute aortic insufficiency and chronic progressive degeneration of valvular tissue. Cholesterol lowering drugs were demonstrated to be able to retard this progression. This review considers prognostic factors for prediction of progressive degenerative processes and novel targets to prevent calcification of aortic valves.