Edward Jenner administers the first smallpox inoculation.

Edward Jenner was an English physician and scientist who pioneered the concept of vaccines and created the smallpox vaccine, the world's first vaccine. The terms vaccine and vaccination are derived from Variolae vaccinae, the term devised by Jenner to denote cowpox. He used it in 1798 in the title of his Inquiry into the Variolae vaccinae known as the Cow Pox, in which he described the protective effect of cowpox against smallpox.

Smallpox was an infectious disease caused by Variola virus, which belongs to the genus Orthopoxvirus. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) certified the global eradication of the disease in 1980, making smallpox the only human disease to have been eradicated to date.

Inoculation is the act of implanting a pathogen or other microbe or virus into a person or other organism. It is a method of artificially inducing immunity against various infectious diseases. The term "inoculation" is also used more generally to refer to intentionally depositing microbes into any growth medium, as into a Petri dish used to culture the microbe, or into food ingredients for making cultured foods such as yoghurt and fermented beverages such as beer and wine. This article is primarily about the use of inoculation for producing immunity against infection. Inoculation has been used to eradicate smallpox and to markedly reduce other infectious diseases such as polio. Although the terms "inoculation", "vaccination", and "immunization" are often used interchangeably, there are important differences. Inoculation is the act of implanting a pathogen or microbe into a person or other recipient; vaccination is the act of implanting or giving someone a vaccine specifically; and immunization is the development of disease resistance that results from the immune system's response to a vaccine or natural infection.