Antibiotic therapy has improved infective endocarditis prognosis. The observance of general rules to choose the more suitable antibiotic drugs, as regard to their effectiveness, pharmacodynamic peculiarities and use, is mandatory. If the infection is due to antibiotic resistant microorganisms, microbiological analyses to estimate the bactericidal effect of the antibiotics, must be carried out. Resistance to penicillins, oligopeptides and aminoglycosides makes endocarditis produced by Enterococcus spp difficult to treat. The identification of patients at risk for infective endocarditis after surgical and invasive instrumental procedures, allows to introduce antibiotic prophylaxis regimens which can reduce the probability of acquiring the disease.