Polymicrobial aerobic/anaerobic bacterial infections occur frequently and have been documented in most anatomic sites in the body. The etiology of these infections is endogenous in that the normal microbial flora that colonize the various mucosal surfaces of the body can be isolated from these infections after trauma to these membranes allowing these organisms access to normally sterile sites. Subsequently, the organisms begin to proliferate, causing extensive tissue damage. These infections may spread to adjacent tissues or become loculated with abscess formation. In patients judged to have severe infection, surgery is often needed to debride the advancing spread of the infection, remove loculated pus, and reestablish sufficient blood flow to deliver appropriate antimicrobial agents to the infected site. Choice of antimicrobial agents should include agents with activity against both aerobes and anaerobes. Although a variety of anaerobes can be isolated from these infections, the Bacteroides fragilis group is the most clinically important group of anaerobes because of the production of virulence factors and the high incidence of beta-lactamase production. Against the various B. fragilis group species, metronidazole remains a very active agent, whereas resistance rates to clindamycin are high among the non-B. fragilis species. Because of the good activity of many cephalosporin/cephamycin agents against aerobic gram-negative bacteria and moderate to good activity against anaerobes, these compounds remain as broad-spectrum choices for use in therapy of mixed infections. The addition of beta-lactamase inhibitors (tazobactam, sulbactam, or clavulanate) to various beta-lactam agents has increased their antimicrobial spectrum against certain groups of aerobes, and particularly against beta-lactamase-producing anaerobes, including the B. fragilis group. The choice of single-agent therapy of mixed infections is ideally based on local data of susceptibility patterns of the various aerobes and anaerobes involved in these infections.