The treatment of many anaerobic infections involves antimicrobial therapy, appropriate surgical drainage of abscesses, and debridement of devitalized tissue. Most anaerobic infections are polymicrobial and require treatment with agents active against an array of aerobic and anaerobic bacteria. Bacterial resistance, especially to penicillins and tetracyclines, but also to newer agents of other classes, continues to increase. As a result, treatment with more than one drug is often required. Combination therapy is often necessary in serious infection, and is indicated for empiric treatment before receiving culture results. In the past combination therapy has been the mainstay of antimicrobial therapy, but more recent studies suggest that monotherapy for anaerobic infections may dominate the future. Selection of an agent requires consideration of the site of infection and the most likely etiologic agents. In vitro susceptibility is important, but it is not the only determinant of antimicrobial effectiveness. The pharmacology of the drug - absorption, distribution, concentrations in body fluids and tissues, excretion and metabolism - also plays an important role. The nature and severity of the underlying illness are important factors in selecting empiric therapy. Although it is a clinical judgement, in patients considered to have mild to moderate infections, several factors in selecting antimicrobial agents may be considered, including cost, whereas in patients judged to have severe or life-threatening infections, the most potent agents should be chosen as initial therapy regardless of cost. Finally, the toxicities of the agent must also be considered.