Rabies is an acute, progressive, incurable viral encephalitis. The causative agents are neurotropic RNA viruses in the family Rhabdoviridae, genus Lyssavirus. Mammalian reservoirs include the Carnivora and Chiroptera, but rabid dogs still pose the greatest hazard worldwide. Viral transmission occurs mainly via animal bite, and once the virus is deposited in peripheral wounds, centripetal passage occurs towards the central nervous system. After viral replication, there is centrifugal spread to major exit portals, the salivary glands. The epidemiological significance of any host “carrier” state remains highly speculative. Although incubation periods average 1–3 months, disease occurrence days or years after exposure has been documented. Rabies should be suspected in patients with a concomitant history of animal bite and traditional clinical presentation, but a lack of such clues makes antemortem diagnosis a challenge. Pathogenetic mechanisms remain poorly understood, and current care entails palliative measures only. Current medical emphasis relies heavily on prevention of exposure and intervention before clinical onset. Prophylaxis encompasses thorough wound treatment, vaccine administration, and inoculation of rabies immunoglobulin. Although it is a major zoonosis, canine rabies can be eliminated, and application of new vaccine technologies permits significant disease control among wildlife species. Nevertheless, despite much technical progress in the past century, rabies is a disease of neglect and presents a modern public-health conundrum.