Virulence is defined as the relative capacity of a microorganism to overcome the defense mechanisms of the host organism and thereby cause disease. Virally induced virulence is usually quantitated by measuring the mean time to death or appearance of symptoms following viral inoculation. In this review we make a distinction between general virulence and neurovirulence. We define neurovirulence as the degree of pathogenesis in the nervous system, but intend it to be more encompassing than the simple ability of the virus to grow in the central nervous system (CNS). This distinction is made possible by recent advances that permit an integrated assessment of the degree of pathology, reactive gliosis, and inflammatory response to infection in the intact organism with specific antisera and molecular probes.