Rabies is a neglected zoonotic disease which kills many people a year, most of them in Africa and Asia. In the majority of developing countries, the number of patients receiving post exposure prophylaxis has steadily increased over time, particularly in urban areas due to dog related rabies. Studies conducted in sub-Saharan Africa show that most of the rabies cases in animals and humans are caused by canine rabies virus, mostly transmitted by domestic dogs and thus comprehensive and sustained dog vaccination is sufficient intervention in reduction and eventual elimination of human rabies in the region. In many developing countries, progress in preventing human rabies through control of the disease in the dog reservoir were slow due to technical, intersectoral, organizational and financial barriers. For developing countries like Ethiopia, strategy should be developed to prevent and control the disease. Sustainable resources for effective dog vaccination are likely to be available through the development of intersectoral financing schemes involving both medical and veterinary sectors. Prevention of animal rabies through dog vaccination, better public awareness, improved access to cost-effective and high-quality human rabies vaccines, and improved local capacity in rabies surveillance and diagnostics are essential for the elimination of human rabies. Generally, elimination of canine rabies is epidemiologically and practically feasible through mass vaccination of domestic dogs which is cost-effective approach to the prevention and elimination of human rabies deaths. The purpose of this paper is to show the burden of the disease and to give direction for effective prevention and control following developed countries experience.