Enterococci are nosocomial pathogens intrinsically resistant to a variety of commonly used antimicrobial agents. The frequent use of antimicrobial agents such as cephalosporins has been associated with the increased isolation of enterococci in pediatric hospitals. In addition to their intrinsic resistance traits, the enterococci have rapidly accumulated a variety of acquired resistance determinants. Strains that are resistant to all currently available antibiotics are now being isolated from infected children. The threat of untreatable enterococcal infection and the possibility that vancomycin resistance may spread from the enterococci to the more virulent pneumococci or staphylococci argue for vigilant surveillance for resistant strains, isolation and barrier precautions for infected patients, increased research into the mechanisms of resistance, and a reinvigorated effort to identify new classes of antimicrobial agents.