Rabies viral encephalitis, though one of the oldest recognized infectious disease remains an incurable, fatal encephalomyelitis despite significant advances in understanding of its pathobiology. Advances in science has led us to the trail of the virus in the host, but the sanctuaries in which the virus remains hidden or “latent” for its survival is unknown. Insights into host-pathogen interactions has facilitated evolving immunologic therapeutic strategies but we are far from finding a cure. To explain dichotomy in clinical presentation and uniform mortality in this viral encephalitis, various factors have been implicated that include both viral and host factors such as neuroanatomical distribution of viral antigen within brain, alteration in host immunity or viral strain in the former whereas apoptosis, neuronal dysfunction and neurotransmitter abnormalities in critical neuroanatomical areas are the popular explanations for the latter. Most of the present day knowledge has however evolved from invitro studies using fixed (attenuated) laboratory strains that may not be applicable in the clinical setting. Much has to be learnt about this elusive virus before effective therapeutic strategies can be evolved. This review attempts to address some of these questions that have remain unanswered in light of knowledge available from recent advances.