During the past 30 years, antibiotic prophylaxis has proved of enormous efficacy in reducing the incidence of surgical wound infections, postoperative morbidity and mortality, the duration of the postoperative period, and the overall cost of surgical treatment. In this paper, the timing and route of administration of antibiotic prophylaxis as well as the dosage and duration, the indications for antibiotic prophylaxis, the importance of the alterations of the delayed hypersensitivity response, and the value of antibiotic prophylaxis for prevention of postoperative septic complications in anergic patients are analyzed. The possibility of combining antibiotic prophylaxis with immunoprophylaxis for high-risk patients is also analyzed.