The management of severe bacterial sepsis is an integral part of intensive care medicine. Early and appropriate treatment with antimicrobials positively affects mortality and significantly reduces the time spent in both intensive care and the hospital. Drug choice is usually made on a "best guess" basis and instituted prior to receipt of appropriate blood, sputum, urine or drainage culture results. Bactericidal drugs should be given in combination, delivered by intravenous bolus and directed towards broad cover of all likely pathogens. Aminoglycoside/ureidopenicillin combinations are synergistic and widely used--often combined with metronidazole. Aminoglycoside toxicity can be reduced by giving the drug once daily (OD) rather than by traditional multiple daily dosing (MDD) and by measuring peak and trough serum levels. Efficacy is increased by attention to the peak serum level/MIC ratio which determines the response to treatment. Several newer agents have been more recently introduced. These drugs include ceftazidime, imipenem/cilastatin, the quinolones and clavulanic acid/semisynthetic penicillin combinations. Other newer drugs currently under evaluation include aztreonam, teicoplanin, the penems and carbapenems.