The clinical and pathological features of the most frequent intrinsic structural diseases that affect the heart valves are well established, but heart valve disease mechanisms are poorly understood, and effective treatment options are evolving. Major advances in the understanding of the structure, function and biology of native valves and the pathobiology, biomaterials and biomedical engineering, and the clinical management of valvular heart disease have occurred over the past several decades. This communication reviews contemporary considerations relative to the pathology of valvular heart disease, including (1) clinical significance and epidemiology of valvular heart disease; (2) functional and dynamic valvular macro-, micro- and ultrastructure; (3) causes, morphology and mechanisms of human valvular heart disease; and (4) pathologic considerations in valve replacement, repair and, potentially, regeneration of the heart valves.