Neurological implications viral illnesses of central nervous system (CNS) are discussed in this chapter. Detailed review of the virology of CNS is beyond the scope of this chapter. Viruses probably account for most cases of acute aseptic meningitis, the most common presentation. Entero virus (mumps) is the most common cause of viral meningitis; others include HSV, HIV, Prions, and JE Virus (arbovirus) are presently important viruses with wider neurological implications. The most common acute viral encephalitis that requires neurosurgical intervention (decompressive craniotomy in rapidly progressive cases) is Herpes simplex (HSV). HSV type 1 is the cause of HSV encephalitis, whereas the type 2 virus is the usual cause of HSV meningitis in adults. The most common post or para infectious viral encephalopathy encountered in neurosurgery is Reye’s syndrome. The most common slow unconventional viral disorder of interest to the neurosurgeons is CJD. Neurologic disorders are among the most frequent and devastating complications of HIV infection, due to direct action of HIV virus or opportunistic infections or secondary to HAART. In some circumstances the viruses may remain in the nervous system for a long period, inciting chronic inflammatory response as in the slow conventional viral disorder, subacute sclerosing panencephalitis (SSPE). Large lesions with mass effect that threaten impending herniation require open biopsy with decompression. Stereotactic biopsy may be required on occasions, especially in cases of a single mass lesion and negative serology.