All lyssaviruses have evolved closely with distinct natural reservoir hosts. The latter are animals species in which a pathogen of an infectious disease are maintained independently. For lyssaviruses, these are a wide range of mammalian species within the Carnivora and Chiroptera (bats) orders with a global distribution.

It is generally accepted that bats are the true primary reservoir hosts of almost all lyssaviruses (see bat rabies). However, unlike all other lyssaviruses, rabies viruses (RABVs) as the type species for lyssaviruses have established multiple independent transmission cycles in a broad range of carnivore host reservoirs, where particular RABV lineages circulate within host conspecifics. From the primary reservoir hosts the virus is sporadically transmitted to domestic animals and to humans.

Of all carnivore host reservoirs the domestic dog is responsible for more than 90% of all human rabies fatalities worldwide.

Typical carnivore host reservoirs for RABV are:

Africa: domestic dog (Canis lupus familiaris), jackals (Canis adustus and C. mesomelas), mongoose (Herpestes spp.)

Middle East and Asia: domestic dog (Canis lupus familiaris), red fox (Vulpes vulpes), ferret badger (Melogale moschata), golden jackals (Canis aureus)

Europe: red fox (Vulpes vulpes), raccoon dog (Nyctereutes procyonoides)

North America: raccoon (Procyon lotor), grey fox (Urocyon cinereoargenteus), striped skunk (Mephitis mephitis), coyote (Canis latrans)

South America: domestic dog (Canis lupus familiaris), crab-eating fox (Cerdocyon  thous), marmoset (Callithrix jacchus)

Caribbean islands: domestic dog (Canis lupus familiaris), small Indian mongoose (Herpestes auropunctatus)

Eurasian and American arctic and subarctic regions: arctic fox (Alopex lagopus)

Within one geographic region different independent infection cycles may occur simultaneously, as in the Americas where raccoons, skunks, red foxes, grey foxes, coyotes and arctic foxes are primary reservoir hosts.