The Balmis Expedition from Spain to the New World in 1806, launched off the heels of Jenner's publication on vaccinia vaccine a few years previously, was likely the world's first eradication initiative. The mission was to eradicate the deadly smallpox from the Americas and beyond. That goal, over a century and half later conceptualized and implemented under the guidance of the World Health Organization (WHO), was eventually realized. The core content of this textbook is designed to reflect the teaching elements of an intensive, one-week eradication course given first to graduate students at the School of Public Health, Johns Hopkins University (JHU) in Baltimore, United States, during the summer of 2012. The faculty of four consisted of the two editors of this textbook; Dr. Ciro de Quadros, former smallpox eradicator in Ethiopia and architect of the original polio eradication strategies; and Dr. D.A. Henderson, former head of the global smallpox eradication initiative, WHO. All four of us spent a full week together lecturing and mentoring JHU graduate students. In 2014, under the direction of Dr. Breman, the course was expanded and provided to graduate students at the Milken Institute School of Public Health, George Washington University. The materials in this textbook reflect the discussions in that course, especially with regards to what the co-editors believe to be the most practical, field relevant experiences and definitions. Given the rapidly changing medical and development world, this textbook highlights essential issues for success, illustrated by disease-specific case studies.