Currently, prophylactic antibiotics have proven effective in lowering the postoperative and postprocedure infection rate following vaginal hysterectomy, emergency cesarean section for the patient in labor, radical hysterectomy, abdominal hysterectomy, pregnancy termination, hysterosalpingogram and intrauterine device insertion. Guidelines for the most effective and safe use are presented. Concerns are raised regarding the widespread prolonged use of prophylactic antibiotics on women in labor to prevent Group B streptococcal infections in newborn children and women with prolonged preterm membrane rupture. There is also an awareness needed of a growing incidence of infections seen in the hospital from community-acquired methicillin-resistant Staphylococcus aureus and Clostridium difficile. These problems have not been addressed by the current prophylactic antibiotic strategies.