Rabies virus (RABV) and RABV-related lyssaviruses are the causative agents of zoonotic viral encephalitis, with a case/fatality ratio approaching 1:1. These viruses are endemic in a number of terrestrial mammals and bat species throughout much of the world. Lyssaviruses (family Rhabdovirus, order Mononegavirales, of which RABV is the type species) are characteristically bullet-shaped particles averaging 75 by 180 nm with a single-stranded, negative-sense RNA genome encoding five proteins. In genome order, these proteins are nucleoprotein (N), which tightly encapsulates the genome; phosphoprotein (P), which was formerly referred to as the nonstructural (NS) protein; matrix (M) protein; glycoprotein (G), the primary target of neutralizing antibodies, which is found spread over the surface of the virus; and polymerase (L), the RNA-dependent RNA polymerase. Genetically and antigenically more diverse in glycoprotein than in nucleoprotein, the different lyssavirus variants are each associated with a particular host species. The major reservoir of RABV in Asia is the dog, historically and currently the cause of most human rabies cases; wildlife, including foxes, coyotes, skunks, raccoons, and bats, carry RABV or RABV-related viruses in diverse geographic regions. Effective vaccines and postexposure prophylaxis (PEP) regimens consisting of active and passive vaccination have been available for some time, and where animal reservoirs of the virus have been controlled by vaccination and PEP is readily available, human rabies is no longer the well-known disease of antiquity. However, in Asia, where dog rabies persists, human rabies is not uncommon, with cases estimated to occur at a rate of over 50,000 a year. Elsewhere, human rabies is sporadic, generally resulting from the bite of an infected dog while a traveler is in a region where rabies is endemic or from an interaction with an infected animal when the possibility of virus transmission is not recognized. As RABV can infect all mammals, the virus may be transmitted between a reservoir species and humans by intermediate species that are not normally associated with rabies, such as cats. However, the more common cause of unrecognized infection is through contact with an infected bat. In such cases, the bite or scratch responsible for the infection may be so minor as to go unnoticed.