The discovery of effective antimicrobial drugs has substantially improved the therapeutic outlook for patients with anaerobic infections. In addition, the pathophysiology of anaerobic infections has been elucidated by comparative antibiotic trials and the use of antibiotic probes in experimental animal models. Facultative bacteria, such as Escherichia coli, are responsible for acute peritonitis and sepsis associated with bowel perforation. Anaerobes, particularly Bacteroides fragilis, play the seminal role in subsequent abscess formation. Treatment of only the facultative bacteria, without adequate antibiotic coverage for anaerobic bacteria, leads to clinical failures with complications of abscess formation. Such therapeutic misadventures have been witnessed in the treatment of mixed infections with cephalosporins and penicillins that lack significant activity against anaerobes. Similarly, use of metronidazole or clindamycin as a single agent is associated with failures caused by infection with facultative bacteria. Mixed infections involve complex interactions between facultative bacteria and strict anaerobes, many of which possess intrinsic pathogenicity. The best therapeutic results are realized with antimicrobial drugs that are active against both types of microorganisms.