Publisher Summary This chapter reviews the rabies pathogenesis and pathology. In majority of rabies cases, the pathologic manifestation in the central nervous system (CNS) is acute encephalomyelitis. The pathologic changes that remain inconspicuous even in the cases with long incubation periods are unique to rabies, suggesting the virus persistence in extraneural organs and/or a lack of host immune responses during the incubation period. The contributions of electron microscopy to rabies research are twofold: it confirms the viral nature of the Negri bodies following the demonstration of the viral antigens in the inclusions by immune-fluorescence, and it elucidates the mode of maturation and the spread of rabies virus within the nervous system. The sporadic occurrence of pyknotic or necrotic neurons and the mild perivascular and subarachnoidal inflammatory cell infiltration—are the main pathologic changes in hematoxylin and eosin-stained sections of the infected brain. Thus, if Negri bodies are absent, then the histopathologic diagnosis of rabies cannot be made.