Prophylaxis of infective endocarditis has been the subject of recommendations from most countries for several years. The basis of the recommendations is the administration of prophylactic antibiotics preceding a procedure at risk for patients with a known at risk cardiac disease. The antimicrobial agent is selected to be active against the main microorganisms causing bacteremia according to the type of at risk procedure. Furthermore, the choice and modalities of antibiotic prophylaxis are adapted to take into account a possible documented allergy to penicillin, the type of predisposing cardiac disease, the number of performed procedures and the requirement for general anesthesia. Future advances should concern the diffusion and application of these recommendations, and the appropriateness of these practices in terms of general cost benefit assessment.