Bacterial colonization of the nasopharynx is a common first step in the development of acute bacterial meningitis and many other kinds of infection. The most common etiologic agents of bacterial meningitis are the pneumococci, meningococci, and group B streptococci. Pneumococcal meningitis is age-dependent, with the highest rates occurring at the extremes of age. A primary goal is to determine whether the patient has bacterial meningitis, specifically meningococcus, because there is the need for Transmission-based Precautions, prophylaxis issue for close contacts, and requirements for reporting to public health departments. Most cases of viral aseptic meningitis are benign and self-limited without indications for Transmission-based Precautions. There are evolving issues regarding infections of ventricular shunts, including difficulty in diagnosis, treatment length/route, surveillance, and newer data that antibiotic-impregnated catheters may have some role in reducing infections. Identifying those patients who could have herpes simplex infection is important, because highly effective antiviral treatment is available. Acute encephalitis may reflect infection with bacteria, viruses, rickettsiae, or fungi, or it may be a noninfectious sequel to a prior infection. Arboviruses are important causes of vectorborne encephalitis for which therapy is limited to supportive care. This includes West Nile virus cases, which have recently been reported throughout the United States. Brain abscess is usually the result of direct extension from a bacterial infection such as sinusitis, otitis, mastoiditis, and dental or facial purulent foci. Spinal or cranial epidural abscesses are commonly the result of metastatic spread from regional sites of purulence. Extraordinary infectious particles called prions are the agents responsible for the four spongiform encephalopathies, namely, Creutzfeldt-Jakob disease, kuru, Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia. Most cases of Creutzfeldt-Jakob disease are sporadic, but much attention has focused on the rare occurrence of a new variant form of Creutzfeldt-Jakob disease, which is caused by a transmissible prion that may be spread via organ/tissue transplantation. Although rare, suspected/confirmed Creutzfeldt-Jakob disease cases raise disinfection/sterilization issues for surgical instrumentation.