Early in the 18 th century, variolation (referred to then as ‘inoculation’) was introduced to Britain and New England to protect people likely to be at risk of infection with smallpox. This triggered a number of important developments. Among them were early examples of what we refer to today as ‘evidence-based medicine’ – immunization, and quantitative measures of disease severity. Establishing the protective effects and subsequent spread of variolation paved the way for recognition that inoculation with cowpox (vaccination) also conferred protection. The definitive experiments that established that vaccination was protective showed that variolation did not ‘take’ following vaccination, thus confirming that immunity had been achieved. Vaccination led ultimately to the eradication of smallpox, one of the great achievements of medicine. Given the central role of variolation in these significant events, it is worth investigating where the practice originated.