Infective endocarditis (IE) continues to be a serious disease with a poor prognosis and high mortality. Neither incidence rates nor mortality have decreased in recent decades. Because of this, it is important to prevent IE in patients at risk. In the past, prevention of IE has focused on antimicrobial prophylaxis, mainly for dental procedures. However, recent major changes in epidemiology, the most significant being the growing frequency and high mortality rate of health care-associated valve endocarditis (HAIE), mean that preventive strategies against IE must also change. Since intravascular catheters are the most common source of bacteremia among patients with HAIE, significant efforts must be made to minimize the risk of catheter-related bloodstream infections. Measures for preventing the infection of prosthetic valves and cardiac implantable devices at the time of implantation also need to be implemented.