OBJECTIVE:: To review the current status of antibiotic prophylaxis for cesarean delivery, emerging strategies to enhance the effectiveness of antibiotic prophylaxis in reducing postcesarean infection, and the implications of the emerging practices. DATA SOURCES:: We conducted a full PubMed (January 1966 to July 2008) search using the key words "cesarean" and "antibiotic prophylaxis." A total of 277 articles were identified and supplemented by a bibliographic search. METHODS OF STUDY SELECTION:: We selected a total of 15 studies, which included all published clinical trials, meta-analyses of clinical trials, and observational studies evaluating either the timing of antibiotics or the use of extended-spectrum prophylaxis. We also reviewed nine reports involving national recommendations or technical reviews supporting current standards for antibiotic prophylaxis. TABULATION, INTEGRATION, AND RESULTS:: We conducted an analytic review and tabulation of selected studies without further meta-analysis. Although current guidelines for antibiotic prophylaxis recommend the administration of narrow-spectrum antibiotics (cefazolin) after clamping of the umbilical cord, the data suggest that antibiotic administration before surgical incision or the use of extended-spectrum regimens (involving azithromycin or metronidazole) after cord clamp may reduce postcesarean maternal infection by up to 50%. However, these two strategies have not been compared with each other. In addition, their effect on neonatal infection or infection with resistant organisms warrants further study. CONCLUSION:: The use of either cefazolin alone before surgical incision or an extended-spectrum regimen after cord clamp seems to be associated with a reduction in postcesarean maternal infection. Confirmatory studies focusing additionally on neonatal outcomes and the effect on resistant organisms, as well as studies comparing both strategies, are needed. © 2009 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins.