Prophylactic administration of antibiotics can decrease postoperative morbidity, shorten hospitalization, and reduce the overall costs attributable to infections. Principles of prophylaxis include providing effective levels of antibiotics in the decisive interval, and, in most instances, limiting the course to intraoperative coverage only. Use in The National Research Council clean contaminated operations is appropriate and, in many instances, has been proven beneficial. Antibiotic prophylaxis is also indicated for clean operations, such as those involved with insertion of prosthetic devices, that are associated with low infection risk and high morbidity. Extension of antibiotic prophylaxis to other categories of clean wounds should be limited to patients with two or more risk factors established by criteria in the study of the efficacy of nosocomial infection control (SENIC) because the baseline infection rate in these patients is high enough to justify their use. Cefazolin (or cefoxitin when anaerobic coverage is necessary) remains the mainstay of prophylactic therapy. Selection of an alternate agent should be based on specific contraindications, local infection control surveillance data, and the results of clinical trials. Newer criteria for determining the risk of "site infection" (wound and intracavitary) are in evolution and may lead to modification of these recommendations over the next several years.