BACKGROUND Infections may complicate cardiovascular surgery or may require surgery as an adjunct to successful treatment. Staphylococci, which are among the major pathogenic bacteria causing such infections, can be resistant to many of the older antibiotics. METHODS The properties of several newer antimicrobial agents, recently approved or still investigational, were reviewed, with an emphasis on in vitro activities against staphylococci. RESULTS The 2 approved agents, linezolid and quinupristin-dalfopristin, and several investigational agents being developed demonstrate in vitro antimicrobial activity against staphylococci. Three of these agents, daptomycin, which was approved by the US Food and Drug Administration in September 2003, and oritavancin and dalbavancin, which are in advanced stages of clinical development, are discussed. CONCLUSIONS Although clinical studies are required, the in vitro anti-staphylococcal activities of several agents suggest that these antimicrobial agents might be useful options for some infections in patients who are intolerant of older antibiotics or who are infected with organisms that are resistant to older agents.