The response of infective endocarditis to antimicrobial therapy is slow because host defence mechanisms in heart valves are absent, high bacterial densities occur in vegetations and the infecting agents have a low metabolic activity. In this situation, only an optimal antibiotic treatment can be effective; therefore early identification of the microorganism by means of blood cultures and the use of bactericidal antibiotics with proven efficacy in clinical trials are essential. The antibiotics should be administered intravenously, because constant and high serum levels are important. The choice of the empirical therapy is based on the patient's history, on clinical signs and symptoms as well as on some additional examinations in order to define the most probable organisms involved. As soon as the infecting agent is identified, the treatment should be optimized. A daily clinical examination of the patient and frequent laboratory controls are needed. In case of poor clinical response to the antimicrobial therapy, the search for complications is frequently more appropriate than changing the antibiotics. The duration of therapy depends on the infecting agent, the evolution and the antibiotic regimen that has been chosen. After treatment, blood cultures should be taken at four and eight weeks, since most relapses appear within this period.