While foot infections in persons with diabetes are initially treated empirically, therapy directed at known causative organisms may improve the outcome. Many studies have reported on the bacteriology of diabetic foot infections (DFIs) over the past 25 years, but the results have varied and have often been contradictory. A number of studies have found that Staphylococcus aureus is the main causative pathogen (12,34,35), but two recent investigations reported a predominance of gram-negative aerobes (20, 47). The role of anaerobes is particularly unclear, because in many studies specimens were not collected or cultured properly to recover these organisms. Among those that did use appropriate methods, some report that anaerobes play a minimal role (2,7,15,21,46), while others suggest that Bacteroides fragilis is the predominant anaerobe isolated (1,3,17,57).These discrepancies could be partly due to differences in the causative organisms occurring over time, geographical variations, or the types and severity of infection included in the studies (1,20,47,51). In addition, some studies used a relatively small number of specimens, failed to report recent or concomitant antibiotic therapy, did not ensure that the specimen collection techniques would exclude superficial or colonizing organisms, or even make clear whether or not the wound was clinically infected. Also, laboratory processing of the samples may have been inadequate to grow anaerobes or fastidious organisms, and protocols that classify potential pathogens (e.g., coagulase-negative staphylococci [CoNS] or Corynebacterium species) as colonizers may have been used (4,46,49).While S. aureus and beta-hemolytic streptococci are widely recognized as pathogens in early DFIs, the role of other frequently isolated organisms is less clear to both the clinician and the microbiology laboratory. Previous studies have shown that when optimal specimen collection, transport, and culture techniques are used, multiple organisms are usually recovered from DFIs (6,14,23,29,30,45,55). Furthermore, some studies suggest that the interactions of organisms within these polymicrobial mixtures lead to the production of virulence factors, such as hemolysins, proteases, and collagenases, as well as short-chain fatty acids, that cause inflammation, impede wound healing, and contribute to the chronicity of the infection (5,52,53,56). In such mixtures, biofilms that impede the penetration of antimicrobial agents into the infected site may also form (25). Thus, the presence of multiple species can have important clinical implications that should not be overlooked (5, 23).