Antibiotic treatment of infective endocarditis has to be discussed when the microorganism has been identified. Antibiotics must be started as soon as possible, just after blood samplings in case of clinical bacteraemia, or as soon as blood cultures are positive. In case of negative blood cultures, diagnosis of endocarditis has to be reconsidered, according to Duke's criteria, and antibiotics must not be started until there is strong evidence in favour of infective endocarditis. Antibiotic treatment must be bactericidal, intravenously administered, for a long time to sterilize vegetations. Duration of antibiotics depends on the microorganism, and whether there is a valvular prosthesis or not. Hospitalization is often mandatory, but there is a trend towards the use of outpatient treatments, only possible in some indications.