Surgical site infection continues to be a major source of morbidity, economic cost, and even death in surgical patients. These infections occur as part of a complex interaction between the number of bacteria that contaminate the surgical site, the virulence of the contaminant, the microenvironment at the surgical site, and the integrity of host defense. Different surgical sites from different types of operations are at different risks for infection. Of importance, acute and chronic medical conditions become important variables in modulating the effectiveness of the host response, and hence the likelihood that infection will occur. The actual rates of surgical site infection for most operations remain poorly defined because many procedures are performed on an outpatient basis, many infections in the inpatient population are not identified until after discharge, and the thoroughness of surveillance remains inconsistent. Multiple preventive measures, including the judicious use of preoperative antibiotics, have been demonstrated to reduce the frequency of surgical site infections. Even with the use of all of the effective preventive measures, infections still occur and require effective management and innovative new strategies to minimize the consequences of the infection.