These are interesting times in the treatment of infections caused by Staphylococcus aureus, with shifting epidemiology of antibiotic resistance; changing prevalence of clinical syndromes (probably reflecting changes in virulence of circulating strains); and the recent availability of a variety of new agents with activity against multidrug-resistant gram-positive cocci. The abundance of riches in new drugs for the multidrug-resistant gram-positive space is timely, and these agents show great potential, but as yet have incompletely tested durability and comparative efficacy. This article reviews the advantages and disadvantages of a variety of antistaphylococcal agents by providing basic information including mechanism of action; mechanisms of resistance; clinical use (including dosing for and data supporting common indications); drug toxicities; and major drug interactions.