Rabies is one of the oldest known pathogens, is incurable, and has the highest fatality rate of all infectious diseases. The Americas is the only region with bat rabies virus, including vampire bat rabies. The region is rich in cultural references and notable for many discoveries in the field, including the current vaccine potency test, diagnostic assay, conception of oral vaccines for wildlife, the first human survivor and the first successful canine rabies program executed at a broad level. Rabies remains the most important viral zoonosis, with tens of thousands of human fatalities and tens of millions of exposures annually, which can be used to model for other pathogens, such as COVID-19. There is an international effort to eliminate human rabies caused by dogs over the next decade, and the Americas represent the primary region with the greatest proof-of-concept evidence to accomplish this goal.