Antimicrobial prophylaxis in surgery refers to a very brief course of an antimicrobial agent initiated just before the start of the procedure. The efficacy of antimicrobials to prevent postoperative infection at the site of surgery (incisional superficial, incisional deep, or organ/space infection) has been demonstrated for many surgical procedures. Nevertheless, the majority of studies centering on the quality of preoperative prophylaxis have found that a high percentage of the antimicrobials used are inappropriate for this purpose. This work discusses the scientific basis for antimicrobial prophylaxis, provides general recommendations for its correct use and specific recommendations for various types of surgery. The guidelines for surgical antimicrobial prophylaxis are based on results from well-designed studies, whenever possible. These guidelines are focussed on reducing the incidence of infection at the surgical site while minimizing the contribution of preoperative administration of antimicrobials to the development of bacterial resistance.