Animal rabies is endemic in Israel, with 50-80 laboratory-confirmed cases being diagnosed annually. Despite the high incidence among animals, human rabies has not occurred in Israel for almost four decades. This is likely due to the highly effective prevention policy implemented by the Ministry of Health, based on pre-exposure vaccination of populations at risk, post-exposure treatment, and updated rules. Notwithstanding the previous success, a human case occurred in 1996 when a soldier was bitten, while asleep, by an unidentified small animal, which according to his description was a rat or a mouse. Since injuries by these rodents do not require antirabies treatment, no antirabies post-exposure prophylaxis was administered. Five weeks later the soldier complained of fever and nausea with interchanging periods of rage and calm, confusion, and water aversion. His condition deteriorated gradually, leading to deep coma and death. Immunofluorescence examination of a skin biopsy was positive for rabies, and PCR of saliva revealed Lyssavirus genotype 1. We review the changes in the epizootiology of rabies in Israel, the trends of human exposure to animals, and the pre- and post-exposure prophylaxis guidelines, and discuss possible measures that could have been undertaken to prevent the eventuality of this case. This case of rabies, the first after a long period without human disease, accentuates the importance of strict adherence to prevention guidelines. Considerations of geography, epidemiology, and the circumstances of exposure are crucial in the treatment decision-making process.