While microbial biofilms have been recognized as being ubiquitous in nature for the past 40 years, it has only been within the past 20 years that clinical practitioners have realized that biofilm play a significant role in both device-related and tissue-based infections. The global impact of surgical site infections (SSIs) is monumental and as many as 80 % of these infections may involve a microbial biofilm. Recent studies suggest that biofilm- producing organisms play a significant role in persistent skin and soft tissue wound infections in the postoperative surgical patient population. Biofilm, on an organizational level, allows bacteria to survive intrinsic and extrinsic defenses that would inactivate the dispersed (planktonic) bacteria. SSIs associated with biomedical implants are notoriously difficult to eradicate using antibiotic regimens that would typically be effective against the same bacteria growing under planktonic conditions. This biofilm-mediated phenomenon is characterized as antimicrobial recalcitrance, which is associated with the survival of a subset of cells including “persister” cells. The ideal method to manage a biofilm-mediated surgical site wound infection is to prevent it from occurring through rational use of antibiotic prophylaxis, adequate skin antisepsis prior to surgery and use of innovative in-situ irrigation procedures; together with antimicrobial suture technology in an effort to promote wound hygiene at the time of closure; once established, biofilm removal remains a significant clinical problem.