Viruses are the most common infectious cause of encephalitis, aseptic meningitis, and myelitis. More than 100 viral pathogens have been identified as causing encephalitis. As newer technologies allow for rapid screening for multiple viruses simultaneously, the list of viral central nervous system (CNS) infections is likely to grow. Numerous non-viral infections and non-infectious processes can mimic viral CNS infection. A systematic approach to viral CNS disease therefore must take into account viral factors, including tropism for certain CNS structures, host factors, including immune status and exposure risk, and targeted testing aimed at the most serious and most likely etiologies. While treatment for most viral CNS infections is supportive, certain inflammatory CNS diseases have drastically different outcomes depending on appropriate and timely treatment and therefore must be distinguished quickly from other viral causes.