During the past decade, there has been a marked increase in the prevalence of community-acquired methicillin-resistant Staphylococcus aureus infection in the United States and elsewhere. The most common such infections are those involving the skin and skin structures. Although a number of these lesions (including small furuncles and abscesses) respond well to surgical incision and drainage, oral antimicrobial agents are commonly used to treat these infections in outpatients. Unfortunately, with the exception of linezolid, none of the agents presently being used in this fashion has been subjected to rigorous clinical trial. Thus, current therapy is based largely on anecdotal evidence. For more-serious infections requiring hospitalization, parenteral antimicrobials such as vancomycin, teicoplanin, daptomycin, linezolid, and tigecycline are presently available and have demonstrated effectiveness in randomized, prospective, double-blind trials.