Because of its severity, it is agreed that infectious endocarditis should be prevented whenever possible. Certain patient populations at risk for endocarditis have been identified. Antibiotic prophylaxis is therefore recommended when these individuals undergo procedures likely to cause bacteremia with organisms that cause endocarditis. In this article we attempt to provide a comprehensive approach to infectious endocarditis prophylaxis based both on the pathophysiology of the disease and on the mechanisms of action of prophylactic drugs. Approaches to the prevention of endocarditis have been recently modified and are reviewed in this paper, especially important issues for the primary care physician.