Although aortic stenosis is a common condition associated with major morbidity, mortality, and health economic costs, there are currently no medical interventions capable of delaying or halting its progression. Re-evaluation of the underlying pathophysiology is therefore required so that novel therapeutic strategies can be developed. Aortic stenosis is characterized by progressive aortic valve narrowing and secondary left ventricular hypertrophy. Both processes are important because in combination they drive the development of symptoms and adverse events that characterize the latter stages of the disease. In this review, the authors examine the pathophysiology of aortic stenosis with respect to both the valve and the myocardium. In particular, the authors focus on the role of inflammation, fibrosis, and calcification in progressive valve narrowing and then examine the development of left ventricular hypertrophy, its subsequent decompensation, and the transition to heart failure. Finally the authors discuss potential therapeutic strategies on the basis of similarities aortic stenosis shares with other pathological conditions.