Staphylococcus aureus strains are well-established pathogens that may cause mild to serious life-threatening disease. Coagulase-negative staphylococci, particularly Staphylococcus epidermidis, also have a pathogenic role in humans and cause infections primarily associated with prosthetic devices and indwelling catheters, whereas Staphylococcus saprophyticus usually causes urinary tract infections. Cefotaxime is a "third-generation" cephalosporin that is stable to the staphylococcal beta-lactamases. In vitro studies over the last 15 years have shown that this parenteral cephalosporin has remained highly active (MIC90 ranges of < or = 2-8 micrograms/ml) against oxacillin-susceptible staphylococci. Cefotaxime therapy of staphylococcal infections has resulted in clinical cure/improvement rates ranging from 78%-100% and bacteriologic eradication rates ranging from 85%-100% in a wide variety of infections. Contrary to contemporary dogma, this "third-generation" cephalosporin appears to be efficacious against staphylococcal infections from a review of 15 years of clinical experience.