Despite the dramatic decline of rheumatic heart disease over the past 5 decades, there has not been a concordant decline in the prevalence of valvular heart disease. Degenerative aortic valve disease (DAVD) has become the most common cause of valvular heart disease in the Western world, causing significant morbidity and mortality. No longer considered a benign consequence of aging, valve calcification is the result of an active process that, much like atherosclerotic vascular disease, is preceded by basement membrane disruption, inflammatory cell infiltration, and lipid deposition and is associated with diabetes, hypercholesterolemia, hypertension, and tobacco use. These realizations, in addition to pathological insights gained from emerging imaging modalities, have lead to the exploration of a variety of therapeutic interventions to delay or prevent the progression of DAVD. Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, angiotensin-converting enzyme, and matrix metalloproteinase have all been studied as potential disease modifiers. Moreover, tissue engineering, aided by emerging stem cell technology, holds immense potential for the treatment of valvular heart disease as adjuncts to surgical interventions. Here we review the epidemiology and pathophysiology of DAVD, in addition to highlighting emerging therapeutic interventions for this growing problem.