Molecular diagnostics includes nucleic acid diagnostics, immunodiagnostics, and proteodiagnostics. Polymerase chain reaction is the basis of most of the kits that are available commercially for the diagnosis of various infectious diseases. The most important uses are in the diagnosis of viral infections of the central nervous system. This clinical article describes the advantages as well as limitations of molecular diagnostics for CNS infections. Standard laboratory techniques such as viral culture and serology provide only circumstantial or retrospective evidence of viral infections of the CNS. Polymerase chain reaction is now considered to be the first-line diagnostic test for viral CNS infections such as herpes encephalitis, enterovirus meningitis, and other viral infections occurring in HIV-infected persons.