Most empyemas occur as a complication of pneumonia or lung abscess, but 15% to 30% occur after thoracic surgery and 10% occur in association with an intraabdominal infection. The bacteriology of empyemas that occur in association with lung infections is often polymicrobial and mixed, containing multiple species of both aerobic and anaerobic bacteria, the latter found in up to 75% of cases. In contrast, empyema following thoracic surgery is more likely to be monomicrobial and caused by common nosocomial pathogens such as Staphylococcus aureus and aerobic gram-negative bacilli. Diffusion of antibiotics into both infected and uninfected pleural fluid is good, but certain agents (aminoglycosides and some beta-lactams) may be inactivated in the presence of pus, low pH, and beta-lactamase enzymes. Single antibiotic agents that are likely to be active against the wide spectrum of potential pathogens include imipenem-cilastatin and ticarcillin-clavulanic acid. Combinations of antibiotics should include an effective agent against anaerobic bacteria (clindamycin, metronidazole) coupled with an agent active against aerobic gram-positive cocci and gram-negative bacilli.