A discussion of the particulars leading to the eradication of smallpox is pertinent to both investigators and the public as the clamor for more "breakthroughs" intensifies. The rational allocation of biomedical research funds is increasingly threatened by disease-advocacy groups and congressional earmarking. An overly simplistic view of how advances truly occur promises only to stunt the growth of researchers and research areas not capable of immediate great breakthroughs. The authors review the contributions of Jenner and his countless predecessors to give a more accurate account of how "overnight medical breakthroughs" truly occur-through years of work conducted by many people, often across several continents. In the public eye, few achievements are regarded with such excitement and awe as the medical breakthrough. Developments such as the discovery of penicillin and the eradication of polio and smallpox have each become a great story built around a singular hero. Edward Jenner, for example, is credited with discovering a means of safely conferring immunity to smallpox. The success of vaccination and subsequent eradication of this disease elevated Jenner to a status in medical history that is rivaled by few. However, the story of the eradication of smallpox does not start or end with the work of Jenner. Men such as Benjamin Jesty and Reverend Cotton Mather as well as unnamed physicians from tenth century China to eighteenth century Turkey also made critical contributions to the crowning achievement. Inoculation to prevent smallpox was commonplace in Europe for generations prior to Jenner's work. Jenner himself was inoculated as a child. In fact, vaccination with cowpox matter was documented in England over 20 years prior to Jenner's work. The authors' review of primary and secondary sources indicates that although Jenner's contribution was significant, it was only one of many. It is extremely rare that a single individual or experiment generates a quantum leap in understanding; this "lone genius" paradigm is potentially injurious to the research process. Wildly unrealistic expectations can only yield unsuccessful scientific investigation, but small steps by investigators supported by an informed public can build toward a giant leap, as the story of smallpox eradication clearly demonstrates.