Varicella zoster virus (VZV) encephalitis has become increasingly prevalent in the era of acquired immunodeficiency syndrome (AIDS), and a widening spectrum of pathological lesions has defined the disease in these and other severely immunosuppressed patients. VZV produces three distinct morphological patterns of brain damage. VZV can cause bland or hemorrhagic infarctions secondary to a large or medium vessel vasculopathy. Deep white matter, ovoid mixed necrotic, and demyelinative lesions occur as a consequence of small vessel vasculopathy, with demyelination dependent on the degree of additional oligodendrocyte infection. Distinctive Cowdry A intra-nuclear viral inclusions are rare in either large or small blood vessels or near infarctions, but are commonly found in glial cells at the edge of the smaller ovoid, demyelinative lesions. Ependymal and periventricular necrosis occurs as a result of vasculopathy of subependymal vessels and secondary infection of ependymal and other glial cells in the periventricular region. To clarify these patterns of VZV encephalitis and shed light on their pathogenesis, the authors have examined all cases of VZV encephalitis seen at our institution since 1984. Additionally, the authors review the extensive literature in an attempt to classify the patterns of VZV encephalitis into (1) large/ medium vessel vasculopathy with bland or hemorrhagic infarctions, (2) small vessel vasculopathy with mixed ischemic/demyelinative lesions, and (3) ventriculitis/periventriculitis. Although one of these three patterns often predominates clinically and radiographically, careful histological examination at autopsy shows mixed features in many cases.