There are still many unanswered questions in the pathogenesis of rabies, but recent progress has been made. During most of the long incubation period of rabies, the virus likely remains close the site of viral entry. Centripetal spread to the central nervous system and spread within the central nervous system occur by fast axonal transport. Neuronal dysfunction, rather than neuronal death, is responsible for the clinical features and fatal outcome in natural rabies. Recent work has changed our perspective on the ecology of rabies virus under particular circumstances in certain species. Hopefully, advances in our understanding of rabies pathogenesis will lead to advances in the treatment of this dreaded disease.