Human rabies cases today are predominantly associated with infection from rabid domestic dogs. Unlike dogs, a common global reservoir species that perpetuates rabies viruses (RABV) within their populations, domestic cats are much less frequently reported or vaccinated. Epidemiologically, cats are important vectors of lyssaviruses but are not viral reservoirs. Typically, cats are incidental hosts only, infected with the predominant lyssavirus in their geographic locale. Human cases associated with rabid cats have occurred in Africa, Asia, Europe and throughout the Americas. As adept, solitary hunters, wild and domestic felids are at risk of lyssavirus infection based upon interactions with infected prey, such as bats, or from transmission by other mesocarnivores, such as rabid dogs, foxes, jackals, raccoons, and skunks. Current veterinary vaccines provide safe and effective immunity in cats against phylogroup I lyssaviruses, such as RABV, but not against divergent lyssaviruses in phylogroups II-IV. With the focus upon the global elimination of canine rabies, the emergence of rabies in cats represents a concerning trend. Clearly, education about the occurrence of rabies in cats needs to be improved, as well as the routine vaccination of cats to reduce the associated risks to public health, agriculture, and conservation biology from a One Health perspective.