Viral infections of the central nervous system are common and manifest as both acute and chronic illnesses in adults and children. In this article we review cells of the healthy nervous system, the types of viruses that infect them, the nervous system's specialized immune response to viral infections, and how this host-virus interaction influences the clinical examination findings. We discuss a diagnostic approach to viral infections of the nervous system, which includes the importance of taking a detailed history of the presenting illness that examines possible routes of exposure to the virus. This history when coupled with the examination findings and targeted investigations should enable the clinician to diagnose both common and obscure viral infections of the nervous system.