Despite advances in medical and surgical management, infective endocarditis remains associated with significant morbidity and mortality. Septic embolization to the brain and other organs is one of the most dreaded complications of infective endocarditis. Given the critical role of platelets in bacterial vegetation formation on cardiac valves or cardiac device leads, antiplatelet agents, including aspirin, have recently generated much interest as adjunctive therapies in cardiovascular infections. In this article, we review the published evidence evaluating the role of platelets in the pathogenesis of cardiovascular infections and the rationale for using antiplatelet agents in these infections.