Antibiotic resistance is an ever-increasing problem in enterococci. These bacteria are remarkable in their ability to acquire and disseminate antibiotic resistance genes by a variety of routes. Since first described in 1979, high-level resistance to gentamicin (MIC, greater than 2,000 micrograms/mL) has spread worldwide and has been responsible for serious infections. Resistance is plasmid-mediated and due to aminoglycoside-modifying enzymes. High-level gentamicin resistance indicates that there will be no synergistic bactericidal activity with penicillin-gentamicin combinations. The epidemiology of nosocomial enterococcal infections is remarkably similar to that of nosocomial infections caused by methicillin-resistant staphylococci and by multidrug-resistant gram-negative bacilli. The most likely way these resistant bacteria are spread among hospital patients is via transient carriage on the hands of hospital personnel. Patient-to-patient and interhospital transmission of strains has been reported recently. However, clonal dissemination is not the cause of the increased frequency of resistant strains, since gentamicin resistance appears in a variety of different conjugative and nonconjugative plasmids in Enterococcus.