The incidence of infective endocarditis (IE) continues to rise in many populations and is typically accompanied by a shift to healthcare -associated staphylococcal species. Despite efforts with aggressive antibiotic therapy and increasing rates of surgical intervention, little progress has been made to reduce mortality. Disease prevention is therefore a crucial part of limiting its effects. Prevention should target each point in the pathogenic triad of IE: initiating bacteremia, adhesion to substrate, and proliferation of pathogenic species. Preventative strategies should focus on at -risk patients undergoing high -risk procedures, and these patients and procedures can now be identified by quantitative risk estimates. The attendant risk resulting from a procedure must then be placed in the perspective of the day -to -day risk, and the resulting balance can inform the benefit of prophylactic antibiotics. Implantable devices are a major risk factor for IE, and novel coatings and designs may be effective in risk reduction. Guidelines differ worldwide and a consensus has yet to be reached on who should receive pre-and periprocedural antibiotics.