Chapter 1 introduces smallpox and, its ultimate nemesis, cowpox. At the beginning of the modern age, a more virulent strain of smallpox spread around the world. Observing that survivors did not take smallpox a second time, many cultures recognised that exposure to a mild case might prove advantageous. The practice of smallpox inoculation, first observed in Istanbul, was the focus of interest in western Europe and was introduced experimentally in the English-speaking world in the 1720s. Though not without risks, inoculation led to advances in understanding contagion and improvements in therapy. It also helped clarify the relationship between similar human and animal diseases. The expansion of inoculation in the eighteenth century revealed individuals whose resistance to smallpox infection was associated with prior cowpox infection. Jenner used inoculation to put the notion that cowpox prevented smallpox to the test. Familiarity with the old practice set the scene for the rapid introduction of cowpox inoculation, a milder intervention.