Prophylactic antibiotics can decrease the incidence of postoperative wound infections in indicated procedures. The accepted indications for administering prophylactic antibiotics have been clean-contaminated procedures and prosthesis insertion, but new indications are evolving that consider wound contamination together with anesthetic risk and relative duration of the operation. A prophylactic antibiotic is chosen on the basis of its activity against endogenous flora likely to be encountered, its toxicity, and its cost, in that order. Potent antibiotics used for serious infections are generally not used for prophylaxis. A maximum dose of a prophylactic antibiotic is given preoperatively so that effective tissue concentration is present at and after the time of incision. In the absence of infection, antibiotics should not be continued beyond the operative day. Regimens for specific procedures are discussed.