Aortic stenosis (AS) is the most frequent valvular heart disease. Severe AS results in concentric left ventricular hypertrophy, and ultimately, the heart dilates and fails. During a long period of time patients remain asymptomatic. In this period a pathology progression should be monitored and effectively thwarted by targeted measures. A cascade of cellular and molecular events leads to chronic degeneration of aortic valves. There are some molecular attributes characteristic for the process of valvular degeneration with clear functional link between shifted cell-cycle control, calcification and tissue remodelling of aortic valves. Bioactivity of implanted bioprosthesis is assumed to result in its dysfunction. Age, gender (females), smoking, Diabetes mellitus, and high cholesterol level dramatically shorten the re-operation time. Therefore, predictive and preventive measures would be highly beneficial, in particular for young female diabetes-predisposed patients. Molecular signature of valvular degeneration is reviewed here with emphases on clinical meaning, risk-assessment, predictive diagnosis, individualised treatments.