Smallpox was the first important disease to be eradicated; it was the success of the Smallpox Eradication Programme that inspired this conference. Several biological reasons favored the eradication of smallpox, the most important of which were probably that recurrent infectivity did not occur, that there was no animal reservoir, and that an effective stable vaccine was available. The importance of smallpox as a disease that travelers might import into countries free of smallpox provided a powerful stimulus for its global eradication. This paper highlights some of the problems associated with the eradication of smallpox in two countries where eradication was difficult, India and Ethiopia, and the measures adopted to overcome the problems. The paper also stresses the importance of the development of methods for the certification of smallpox eradication from countries, from regions, and finally from the whole world. It is noted that close links between field work and research were important throughout the eradication campaign.