Mixed infections are usually caused by a relatively limited range of bacteria, with the anaerobes and opportunistic pathogens contributing to their severity. In order to make the best therapeutic choice for a patient with a life-threatening infection, which is probably of mixed etiology, clinicians must be aware of the organisms that are likely to be involved, and the fact that most of them will produce β-lactamase. Of the options available for empiric therapy, the β-lactam/β-lactamase inhibitor combinations represent a good choice. Their antibacterial spectra include both aerobic and anaerobic pathogens. Five combinations are available in clinical practice: ampicillin-sulbactam, piperacillin-tazobactam, ticarcillin-clavulanic acid, amoxicillin-clavulanic acid, and cefoperazone-sulbactam. More strains of clinically important anaerobic bacteria are susceptible to ampicillin-sulbactam than to either piperacillin-tazobactam or ticarcillin-clavulanic acid, which are also available widely and suitable for more life-threatening infections. In addition, sulbactam itself has the highest intrinsic activity of the β-lactamase inhibitors against the opportunistic pathogen, Acinetobacter baumannii. Thus, ampicillin-sulbactam could be considered a drug of choice for the empirical treatment of mixed infections where there is a reasonable possibility of the presence of A. baumannii.