Abstract: Animal genetic resource diversity ensures the continuity of biodiversity and their survival as adaptation to several challenges and agro-ecologies. Animal biodiversity has valuable contribution in animal products variety and to their ecological balance. Currently, animals and their genetic diversity are being under several threats, challenging their sustainability and survival. Infectious diseases are emerged as a potential threat to several animal species and breeds, particularly challenging endangered or at risk animal species/breeds. There are many animal diseases which are contagious, virulent and epizootics inducing dramatic mortality and morbidity in both domestic and wild animal population. Invasive infectious diseases are spreading to susceptible populations unaffected before including to species already being threatened by other factors. Emerged infectious diseases are already been involved in the extinction of some species while threatening exist in most of animal species. Generally, animal epizootics affect about 5% of globally threatened birds (67 species) and 26 species (3%) of threatened mammals are impacted by infectious disease. However, huge impact is observed in amphibians that are particularly affected by disease with 17% (317 species). Different animal diseases possess a significant threat and can wipe out most or entire susceptible animal breed/species or multi-species. Rinderpest, Anthrax, African horse sickness, Avian influenza, Newcastle disease, Rabies, Canine distemper, chytridiomycosis, etc., all these can highly threat susceptible animal species/breed. Rinderpest and rabies with canine distemper has threatened Ethiopian cattle population and the endangered Ethiopian wolf, respectively while anthrax outbreak caused threats in herbivores population’s at Mago National Park. Infectious diseases are one of the constraints in the survival and conservation effort of animal genetic resource diversity. Therefore, organized diseases surveillance and control strategies should be employed to safeguard the sustainability of animal biodiversity. Furthermore, advanced studies are required to clarify current distribution and intensity of diseases impact on global animal biodiversity.