The movement of drugs from the systemic circulation into the central nervous system is restricted by several factors, including the blood-brain and blood-CSF barriers, an active transport system that affects primarily the beta-lactam antibiotics, and the high degree of serum protein binding of certain agents. The functions of the blood-brain and blood-CSF barriers and of the active transport system are reduced but not abolished by inflammation. For most antimicrobial agents, the major determinant of passage aside from serum protein binding is the degree of lipid-solubility of the drug. The beta-lactam and aminoglycoside antibiotics and vancomycin penetrate the central nervous system relatively poorly, whereas chloramphenicol, metronidazole, the fluoroquinolones and trimethoprim-sulfamethoxazole fare better. Knowledge of the relative capacity of various drugs to penetrate the central nervous system after systemic administration may help the physician to choose an optimum regimen for the treatment of bacterial meningitis and brain abscess.