Beginning in 1955, the American Heart Association recommended antibiotic prophylaxis among patients with certain structural heart diseases to decrease the likelihood of infective endocarditis (IE) following dental procedures. Over the ensuing 52 years, the American College of Cardiology/American Heart Association (ACC/AHA) guidelines were revised to address gastrointestinal and genitourinary procedures and to modify the assessment of relative risks and specific regimens for prophylaxis. Throughout the various revisions, prophylaxis was recommended for individuals who were at increased risk of developing IE based on best evidence and consensus opinion, albeit in the absence of randomized controlled trials. In 2007, the AHA published a revised guideline statement dramatically restricting its recommendations for antibiotic prophylaxis against IE. In 2008, these views were incorporated in an ACC/AHA guideline update on the management of patients with heart valve disease. The revisions represent a dramatic shift in terms of the patients for whom antibiotic prophylaxis is recommended and the procedures for which it is recommended. What is striking about the new guidelines is that the change in recommendations was based not on new data, but on a change in philosophy despite the lack of new data. To some degree, the arguments for and against antibiotic prophylaxis become those of philosophy, ethics, and the role of evidence-based medicine. This manuscript attempts to briefly examine those arguments and discuss why the revised guidelines may fail to respect the ethical principles of beneficence and patient autonomy.