The chemistry, pharmacology, microbiology, pharmacokinetics, clinical efficacy, and adverse effects of sulbactam are reviewed. Sulbactam is a competitive, irreversible beta-lactamase inhibitor. Its binding to penicillin-binding proteins imparts weak intrinsic antibacterial activity. Synergy of sulbactam with beta-lactam antibiotics is most marked in bacterial species in which beta lactamase is a major mechanism of resistance. Sulbactam sodium is available in combination with ampicillin sodium for injection in a 1:2 ratio of sulbactam to ampicillin. Sultamicillin, an oral prodrug that is hydrolyzed to equimolar amounts of ampicillin and sulbactam, is in clinical trials. Ampicillin and sulbactam have similar pharmacokinetic properties. Sulbactam-ampicillin appears to be most useful for the treatment of polymicrobial aerobic or anaerobic infections and uncomplicated gonorrhea. Persistence, relapse, and superinfections have been reported after sulbactam-ampicillin treatment of urinary-tract and respiratory-tract infections. The combination is not effective against pseudomonal infections. Sulbactam-ampicillin is generally well tolerated. By restoring or expanding the activity of older, well-established beta-lactam antibiotics, sulbactam offers a new approach to the management of bacterial infections; the minimal toxicity of sulbactam-ampicillin makes the combination appealing for the treatment of gram-negative nonpseudomonal and anaerobic infections.