Wound infection remains a considerable cause of morbidity and mortality among surgical patients, despite the relative success of prophylactic antibiotics. In modern efforts to control healthcare costs while improving the quality of patient care, we must not overlook the basic principles of wound infections and their appropriate treatment. Predisposing factors for the development of surgical wound infection include the creation of a surgical wound, the presence of bacteria, and a susceptible host. The selection of an appropriate antimicrobial drug depends on the identification of the most likely pathogens associated with a given procedure, as well as the expected antibiotic susceptibility of those pathogens. Ideally, a prophylactic antibiotic should achieve high peak tissue concentration at the site of the wound before the first incision and should be maintained until the time of closure. Currently, the administration of prophylactic antibiotics is indicated for contaminated and clean-contaminated wounds. Despite the proven effectiveness of antibiotic prophylaxis, many researchers would argue that contemporary dosing regimens should be reevaluated. The debates concerning the dosage and timing of ideal prophylactic administration are likely to continue.