Enterococci have emerged as a major nosocomial pathogen and as an ever-increasing problem in antimicrobial resistance. They are ubiquitous in the intestinal flora of humans and animals and inherently resistant to a wide array of antimicrobial agents, and, more alarmingly, they seem to have a potential facility for acquiring new resistance determinants, including β-lactamase production, high-level resistance to aminoglycosides, and recently, glycopeptide resistance. Collectively, all of these properties make enterococci one of most difficult nosocomial pathogens to treat and control today. The purpose of this review was to examine the epidemiology, the mechanisms, and laboratory detection of resistance of enterococci to the two major groups of antibiotics: aminoglycosides and glycopeptides.