Laboratory techniques for the diagnosis of central nervous system (CNS) infections are rapidly improving but at present have limitations that necessitate our guarded enthusiasm. Enteroviruses are the most common infectious agents of viral meningitis for which an etiology can be determined, and it is anticipated that the use of the reverse transcriptase polymerase chain reaction (RT-PCR) technique should significantly improve the identification of the etiologic agent of aseptic meningitis. The combination of the polymerase chain reaction technique with laboratory methods for the determination of intrathecal antibody production to herpes simplex virus and varicella-zoster virus have improved the rapidity with which these viral infections can be diagnosed. The pearls and pitfalls of the use of these laboratory techniques in the diagnosis of viral meningitis, recurrent meningitis, and focal encephalitis are included. Recommendations for the empiric therapy of bacterial meningitis in children and adults have changed because of the emergence of penicillin and cephalosporin-resistant pneumococcal organisms. The currently recommended antibiotics and their dosages are included. The evidence for the efficacy of dexamethasone therapy in bacterial meningitis is provided. Meningitis due to Mycobacterium tuberculosis is increasingly recognized, and the initiation of empiric antituberculous chemotherapy should not await the results of CSF cultures. Toxoplasma encephalitis and primary CNS lymphoma are the most common cause of mass lesions in patients with HIV, and the diagnostic techniques to distinguish between these two infections is reviewed. A short discussion of the best test for the diagnosis of neurosyphilis is provided.