Perioperative antibiotic treatment significantly reduces the risk of postoperative wound infection and is cost-effective in clean-contaminated head and neck operations. A clear consensus on the most suitable single agent or combination is, however, lacking. Most surgical wound infections involve both gram-positive and gram-negative aerobes and anaerobes; some organisms may exhibit antibiotic resistance through beta-lactamase production. Comparative trials have indicated that combinations with both aerobic and anaerobic activity provide protection superior to that achieved with single agents active against only aerobic pathogens. Recent results suggest that the beta-lactam/beta-lactamase-inhibitor combination ampi-cillin/sulbactam is cost-effective for perioperative treatment of patients undergoing head and neck surgery.