The paper presents the most recent recommendations for the treatment and prevention of infective endocarditis (IE). The treatment of IE is complex and requires close collaboration among specialists in infectious diseases, cardiology, cardiac surgery and microbiology. The mainstay of medical treatment is antibiotic therapy. Theoretical considerations regarding vegetations and antibiotics have practical consequences on the route and modalities of administration of antibiotics and on the techniques used to monitor treatment. The choice of antibiotics depends on the microorganism (streptococci, enterococci, staphylococci, HACEK group [Haemophilus sp., Actinobacillus sp., Cardiobacterium sp., Eikenella sp. and Kingella sp.], Coxiella, Brucella, Legionella, Bartonella, fungi) and on whether IE occurs on native or prosthetic valves. Treatment of IE with negative blood cultures is particularly difficult. Cardiac surgery is often needed during the bacteriologically active period (in ~50% of patients). The decision to intervene and the optimal timing of the intervention requires careful consideration of multiple potential risks: the haemodynamic risk, the infectious risk, the risk due to cardiac lesions, the risk due to extracardiac complications and the risk due to the location of infective endocarditis. Even though the efficacy of antibiotic prophylaxis of IE is not completely proven, it is recommended for selected patients who undergo an at-risk procedure. Lists of cardiac conditions and of medical procedures at risk are presented; specific antibiotic prophylactic regimens for dental and upper respiratory tract procedures in out-patients, procedures under general anaesthesia and urological and GI procedures are outlined.