Classical virologists defined a number of viruses that affect the nervous system and identified tissue tropism, extraneural replication, and viremia as important parameters that determine whether viral infections will affect the central nervous system. Molecular techniques are expanding this knowledge by permitting us to relate specific genes and gene products to two defined phenotypes: neuroinvasion and neurovirulence. Two converging situations make this knowledge particularly useful: (1) the development of antiviral drugs and subunit vaccines, which mandate that pathogenesis be related to specific regions of the viral genome; and (2) the expanding problem of central nervous system infections in immunodeficient states.