Preventing infections at operative sites has long been a goal of gynecologic and obstetric surgeons. These infections constitute the leading cause of morbidity after both elective and emergent surgical procedures. Serious sequelae such as bacteremia, septic shock, phlegmon, pelvic abscess, septic pelvic thrombophlebitis, wound abscess, and fascial dehiscence may complicate primary infections, with devastating results. Early attempts to prevent postoperative infections concentrated on aseptic techniques and the modification of surgical skills. Soon after the introduction of antibiotics into clinical medicine, surgeons began to administer these drugs to clinically uninfected women to prevent operative-site infection; that practice has been documented and assessed in a large volume of literature. This article reviews the chronologic development of prospective data in the areas of benign gynecology, obstetrics, gynecologic oncology, and infertility and makes recommendations regarding antibiotic prophylaxis of infections associated with surgical procedures.