Numerous important observations concerning the pathogenesis of infective endocarditis have been made over the past 18 years. Many of these observations have been obtained with animal models of endocarditis in which an indwelling catheter has been used to produce predisposing endocardial lesions for subsequent infection. Unlike several previously used animal models, the catheter-induced endocarditis models have many characteristics similar to infective endocarditis in humans. Key findings regarding microbial adherence and persistence and the host response to endocardial infection have led to a better appreciation of the complex issues operative in the pathogenesis of endocarditis.