Rabies, a millennia-old viral infection transmitted through animal bites, poses a lethal threat to humans, with a historic fatality rate of 100% if left untreated. Louis Pasteur's introduction of the rabies vaccine in 1885 marked a turning point in the battle against rabies, preventing numerous cases. The purpose of this paper is to review the historical development, current challenges, and future prospects of rabies vaccination and treatment, with emphasis on the importance of continued research and collaborative efforts in the quest to eradicate this deadly infection. Historical vaccine development progressed from inactivated to live-attenuated forms, with modern recombinant techniques showing promise. The preventive measures at present primarily involve vaccination, but challenges persist, such as differing safety profiles and immunogenicity among vaccine types. Pre-exposure prophylaxis with a three-dose vaccine series is crucial, especially in high-risk scenarios. Post-exposure prophylaxis combines human rabies immunoglobulin and inactivated rabies virus vaccine. The quest for the next generation of vaccines explores genetically modified and viral vector-based approaches; emerging treatments include gene therapy, virus-like particles, and monoclonal antibodies, offering hope for improved outcomes. Economic barriers to post-exposure prophylaxis, limited education, and awareness challenge rabies control. Cost-effective solutions and comprehensive awareness campaigns are vital for the successful eradication of rabies. More research and collaborative endeavors remain pivotal in the ongoing journey to eradicate rabies, one of the deadliest infectious diseases known to humans, if not met with prophylactic measures.