Rabies is a zoonotic disease that is usually transmitted via virus-containing saliva from the bite of an infected animal. The virus infects the central nervous system, resulting in an acute, progressive, fatal encephalomyelitis. Although rabies in domestic animals has significantly decreased in the United States since the mid-20th century, rabies in terrestrial wildlife and bats in the United States and other developed countries, as well as canine rabies in developing countries, continues to present risk for human infections. Human infections can be prevented through avoiding exposure to rabid animals, pre-exposure rabies vaccination of individuals in high-risk occupations, and postexposure prophylaxis (vaccination and rabies immunoglobulin administration) for individuals with exposure with high risk for rabies virus transmission.