In spite of the progress in surgical technique and antibiotic prophylaxis, postoperative infection still accounts for both the commonest surgical complication and one of the most frequent nosocomial infections, also causing an increase in duration and costs of hospital stay. The choice of treatment for post-surgical infections requires an understanding of the usual infecting flora, available antimicrobial agents, and susceptibility patterns. The most common organisms in simple wound infection are gram-positive cocci and mainly Staphylococcus aureus. Staphylococcus epidermidis and S. aureus (quite often methicillin-resistant strains) are the organisms which predominate in the infectious complications following clean surgical procedures with implantation of vascular grafts or prosthetic devices. Mixed aerobic and anaerobic flora are mainly responsible for cases of intra-abdominal and intra-pelvic postoperative infections: the most common aerobes are Enterobacteriaceae (Escherichia coli, Proteus spp., and others) and enterococci, and among anaerobes Bacteroides fragilis group prevails. Adequate drainage and surgical control of the source of infection, when needed, and adjunctive effective antimicrobial therapy are important factors in successful treatment of postoperative infections. Semisynthetic penicillinase-resistant penicillins and glycopeptides (vancomycin and teicoplanin) are the drugs of choice for the treatment of infections caused by penicillin-resistant methicillin-sensitive, and methicillin-resistant, respectively, S. aureus and S. epidermidis. For the treatment of intra-abdominal and intra-pelvic infections, animal and human studies support the recommendation that treatment should be directed against both gram-negative enteric and anaerobic bacteria. Combinations of aminoglycosides with clindamycin or metronidazole have been widely used with great success; however adverse reactions such as nephrotoxicity and ototoxicity have been a problem in some patients. In recent years monotherapy with either a carbapenem (imipenem/cilastatin or meropenem) or a penicillin/beta-lactamase inhibitor combination has been proposed. Among these combination antimicrobials, piperacillin combined with tazobactam is a very well designed formulation. Indeed, piperacillin is active against a broad range of gram-negative and gram-positive pathogens, and tazobactam is a potent beta-lactamase inhibitor which acts on a variety of clinically important plasmid and chromosomal beta-lactamases. This combination seems particularly attractive for the treatment of mixed polymicrobial anaerobic-aerobic infections such as intra-abdominal and intra-pelvic postoperative infections.