Staphylococci have developed a variety of strategies for dealing with the presence of antibiotics encountered in clinical environments. Resistance to beta-lactams and other antimicrobial agents has been accomplished by a diverse array of molecular mechanisms. Options available to treat infections caused by staphylococci resistant to methicillin are limited, and the next generation of antibiotics to be introduced, should glycopeptide resistance become an important clinical problem, is not yet on the horizon.