Rabies is a deadly Neglected zoonotic disease that affects the central nervous system of all warm-blooded animals and is widespread in many regions of the world. It is caused by rabies virus belongs to genus Lyssavirus (“, lyssa”,meaning “, madness”, ), family Rhabdoviridae, and order Mononegavirales. Rabies is a devastating disease endemic in developing countries that is responsible for the death of thousands of lives every year,more than 95% of them are from Africa and Asia. Ethiopia is one of the highest human deaths due to rabies from Africa, even though the cases are under-reported. Rabies is almost fatal once clinical signs and symptoms are developed for both animals and humans. There are different modes of rabies transmission,the most common one is by being bitten by infected hosts and transferring rabies virus contained saliva through the exposure of wound or scratched skin. Domestic dogs serve as a major reservoir of the rabies virus in many developing countries and play a great role in virus transmission. Several countries that apply successful rabies elimination programs perform free post-exposure prophylaxis (PEP) for bite victims and mass dog vaccination, establish a strong national rabies surveillance system, and encourage the capacity of medical staff through sustainable training. Implementing these best experiences toward rabies elimination and dealing with great emphasis in Ethiopia is essential to avoid dog-mediated rabies deaths. In developing countries like Ethiopia, where dog-mediated rabies is endemic, execute dog vaccination policies at regional and municipal levels to break the transmission chains of rabies due to dog bites. Therefore, the government points up sustainable strong inter-sectoral collaboration and community engagement, as well as it provides safe, effective, and affordable modern anti-rabies vaccine to be used for post-exposure prophylaxis to eliminate this public health important disease.