Infective endocarditis (IE) is associated with significant morbidity and mortality. The prevention of infective endocarditis, for many years, has involved the identification of at risk patients undergoing medical or dental procedures and the use of pre-procedural antibiotic prophylaxis. However, evidence regarding the effectiveness of such measures is lacking while evidence is mounting for the adverse effects of inappropriate antibiotic use. International guidelines for antibiotic prophylaxis were amended, radically in some cases to reflect this. Subsequent epidemiological observations of IE have shown mixed results, strengthening calls for well conducted randomised control trials, now that there is genuine clinical equipoise among clinicians about this question.