Antibiotic-resistant enterococci have become an increasingly important cause of nosocomial infections, frequently involved in hospital outbreaks. Acquired antibiotic resistance among enterococci include high-level aminoglycosides, β-lactams and glycopeptide resistance. Vancomycin-resistant enterococci (VRE) have had a major impact in the USA and are now widely distributed among different European countries. The treatment of VRE infections is usually difficult and relatively inefficient, leading to failure of antibiotic therapy and surgery for uncontrolled sepsis. Since there is often no therapeutic agent available of established efficacy for patients infected by VRE, in vitro studies and animal models represent useful tools to test new antibiotic molecules and to evaluate the efficacy of new antibiotics given alone or in association.