Enterococci, most often Enterococcus faecalis, cause 5%-20% of cases of infective endocarditis (IE). Enterococcal IE is usually a disease of older men, and the most frequent source of infection is the genitourinary tract. In cases of enterococcal IE, both normal and previously damaged valves can be involved. The disease most commonly presents in a subacute fashion; clinical and laboratory features are similar to those observed with IE caused by other pathogens. Diagnosis is based on the presence of clinical criteria of IE in association with positive blood cultures. Optimal therapy entails the parenteral use of a cell wall-active agent (penicillin G, ampicillin, or vancomycin) in combination with streptomycin or gentamicin in cases caused by enterococcal strains with high-level resistance to streptomycin. A 4-week treatment course may be adequate in many cases. In patients with streptomycin-resistant strains, mitral valve disease, illness of greater than 3 months' duration, and/or relapse after previous therapy, a 6-week treatment course should probably be administered. With standard treatment and the appropriate use of valve replacement, a cure rate of approximately 85% can be expected.