Staphylococcus aureus continues to be a common pathogen from community-acquired infections and for infections after surgical procedures. A review of the history of this pathogen indicates that it will likely continue to develop new virulence characteristics and that it will continue to develop new patterns of resistance. This presentation addresses the three major areas for surgeons in the future. First, vancomycin is losing its effectiveness against methicillin-resistant S. aureus (MRSA). The future antibiotic choices for treating this pathogen are discussed. Second, vancomycin is losing its effectiveness for prevention of MRSA infections at the surgical site, and another antibiotic choice needs to be developed for prevention of both methicillin-sensitive and methicillin-resistant staphylococci. Third, decolonization of staphylococci from the nasopharynx is discussed commonly in the literature, but valid evidence for this practice is limited. Controlled clinical trials to prevent surgical site infection by decolonization with mupirocin or other agents are needed. In summary, S. aureus will continue to challenge surgeons as an adaptable pathogen that can defy all of our treatment efforts.