A number of antimicrobial agents are useful clinically for the treatment of anaerobic infections. Those most frequently used include the penicillins, especially penicillin G, the cephalosporins and some of their derivatives, erythromycin, clindamycin, chloramphenicol, metronidazole, and vancomycin. The present study was carried out to compare the efficacy of these antimicrobial agents based on five criteria. Antibacterial spectrum against various anaerobic organisms, of which Bacteroides fragilis is a notable representative, was the most important criterion. The bacterial resistance mechanism was our second criterion, primarily the production of enzymes of which the beta-lactamases are the prototype, as well as cell permeability alterations; although these determinations appear mostly to be a chromosomal factor, actual resistance factor plasmids have been discovered. Possible adverse effects were also carefully observed since some of these agents may cause anaphylactic shock, such as produced by the penicillins, or ulcerative colitis, which may endanger the patient's life. The pharmacokinetic profile was the fourth criterion, particularly since tissue diffusion differs so widely among these agents. Finally, the cost factor was carefully evaluated. This study concludes with a discussion relative to the principal indications of these agents for the most commonly encountered anaerobic infections seen in clinical practice.