The therapeutic approach to acute bacterial meningitis has changed in recent years as a result of changes in in vitro susceptibility of many meningeal pathogens to previously standard antimicrobial therapy. Given the emergence of strains of Streptococcus pneumoniae that are resistant to penicillin and the cephalosporins, the combination of vancomycin plus a third-generation cephalosporin is recommended as empiric therapy for suspected or proven pneumococcal meningitis, pending results of in vitro susceptibility testing. Strains of Neisseria meningitidis with reduced susceptibility to penicillin have also been described, although most patients with these resistant strains have recovered with standard penicillin therapy. Although the third-generation cephalosporins have greatly improved outcome in patients with meningitis caused by aerobic gram-negative bacilli, many organisms in this group are now resistant to these drugs; the carbapenems and fluoroquinolones may be effective alternative agents and have been successfully used in small case series. Further surveillance of the in vitro antimicrobial susceptibility patterns of meningeal pathogens is critical for future recommendations in the treatment of bacterial meningitis.