The pathogenesis of infective endocarditis depends on complex interactions between the causative pathogen, plasma proteins, platelets, and vascular endothelial cells. In addition to being the main target of bacteria in the initial stage of bacterial adherence to the endocardium, platelets now appear to play an important role in antimicrobial host defense against endocarditis through the secretion of so-called platelet microbicidal proteins. In animal models of endocarditis, low-dose aspirin was shown to significantly reduce the vegetation weight, the bacterial density of vegetation, the hematogenous bacterial dissemination, and the frequency of embolic events. However, these facts cannot be extrapolated to clinical care in humans, since to date, there is no definitive proof of the adjunctive benefit of aspirin in human infective endocarditis.