During the past decade there have been major changes in the susceptibility of bacteria that cause surgical infections. Resistance to common bacteria is worldwide, both in developed and developing countries. Almost all species of bacteria can develop resistance to antimicrobial agents, and resistance can readily be transferred among bacteria by transmissible elements called plasmids. One of the most important forms of resistance has been the inactivation of antibiotics, particularly penicillins and cephalosporins. The organisms involved in surgical infections include staphylococci, streptococci, enterococci, members of the Enterobacteriaceae, Pseudomonads, and anaerobes. Today virtually all Staphylococcus aureus are resistant to penicillins. Coagulase-negative staphylococci are also increasingly important causes of infection, particularly in cardiovascular surgery, where they may cause serious postoperative complications. Like S aureus, coagulase-negative staphylococci, primarily S epidermidis, also produce beta-lactamases and can be resistant to all beta-lactam antibiotics because of altered penicillin-binding proteins. New beta-lactamases, which destroy extended-spectrum beta-lactam antibiotics, have developed in Enterobacteriaceae, and all Pseudomonas spp. possess beta-lactamases. Various techniques have been used to overcome resistance, one of which is the development of beta-lactamase inhibitors. Currently there are three compounds that are effective inhibitors of many beta-lactamases: clavulanate, sulbactam, and tazobactam. The problem of resistance in surgical infections will not disappear. Increasingly complex operations will be done on more debilitated patients. The development of beta-lactamase inhibitors combined with highly active beta-lactam antibiotics has provided a way of overcoming this form of resistance.