ABSTRACT: The use of antibiotics to prevent infections during the antepartum, intrapartum, and postpartum periods is different than the use of antibiotics to treat established infections. For many years, the use of prophylactic antibiotics was thought to have few adverse consequences. Concerns about the emergence of resistant strains of common bacteria, in addition to the emergence of strains with increased virulence, have resulted in increased scrutiny of the use of antibiotics, particularly in the hospital setting. Awareness of the potential adverse effects of resistant bacterial infections on neonates has been growing. Attention has been focused on the effect of mode of delivery or early antibiotic exposure on the neonatal oral and gut microbiome, which is essential for immune development. Finally, cost is a consideration in the use and choice of prophylactic agents. The purpose of this Practice Bulletin is to present a review of clinical situations in which prophylactic antibiotics are frequently prescribed and to weigh the evidence that supports the use of antibiotics in these scenarios. This Practice Bulletin is updated to reflect a limited change to clarify and provide additional information on recommendations from recent consensus guidelines for antimicrobial prophylaxis in surgery and the prevention of surgical site infection. The following practices related to cesarean delivery include preoperative skin and vaginal cleansing, weight-based dosage for cefazolin antibiotic prophylaxis, the addition of adjunctive azithromycin antibiotic prophylaxis, and antibiotic selection and dosage for women with a penicillin allergy.