In general, virus infections of the brain are rather rare in the immune competent host. However, neurotropic viruses have developed mechanisms to exploit weaknesses in immunological defense mechanisms that eventually allow them to reach and infect CNS neurons. Once in the CNS, these viruses can induce significant neuronal dysfunction and degeneration of specific neuronal populations, sometimes leading to devastating, life-threatening consequences for the host. Here, we examine viruses with the ability to infect neurons and their resulting pathologies, their modes of entry to the CNS, and the cellular and molecular alterations that these viruses induce in neuronal cells. We also discuss the importance of various pathogenic events associated with viral infection of neurons and elaborate on the implications of recent findings suggesting that neuronal cells affected by viruses undergo a "dying back" pattern of degeneration. Finally, findings of virus-induced alterations in kinase activity are discussed in the context of recent evidence linking abnormalities in kinase signaling to the pathogenesis of major human neurodegenerative conditions.