The principles of pathogenesis of infective endocarditis are reviewed. Predisposing factors include not only rheumatic and congenital, but also degenerative cardiopathies, such as valvulopathy, and some extracardial factors of increasing importance. These abnormalities promote the development of nonbacterial thrombotic vegetations, which may become infected when bacteremia occurs. The ability of some microorganisms to produce an infective endocarditis is related to their capacity of adherence to valvular tissue. The pathogenesis of the infected vegetations explains most of the pathophysiologic mechanisms responsible for the variety of the clinical manifestations of infective endocarditis.