Surgical site infections are among the most common serious perioperative complications. Infections are established during a decisive period that lasts a few hours after contamination. Adequacy of host immune defenses is the primary factor that determines whether inevitably wound contamination progresses into a clinical infection. As it turns out, many determinants of infection risk are under the direct control of anesthesiologists; factors that are at least as important as prophylactic antibiotics. Major outcome studies demonstrate that the risk of surgical wound infection is reduced threefold simply by keeping patients normothermic. Infection risk is reduced by an additional factor of two by if supplemental oxygen is provided (80% versus 30%) during surgery and for the initial hours after surgery. The contribution, if any, of other factors including, tight glucose control, fluid management, and mild hypercapnia have yet to be suitably tested.