Smallpox was a serious and deadly viral infection that was eradicated in 1980.Smallpox dates back at least 3,000 years. Efforts to eradicate the disease began in the mid-20th century, with the last naturally occurring case reported in 1977.

Smallpox was a terrible disease. On average, 3 out of every 10 people who got it died. People who survived usually had scars, which were sometimes severe. One of the first methods for controlling smallpox was variolation, a process named after the virus that causes smallpox (variola virus). During variolation, people who had never had smallpox were exposed to material from smallpox sores (pustules) by scratching the material into their arm or inhaling it through the nose. After variolation, people usually developed the symptoms associated with smallpox, such as fever and a rash. However, fewer people died from variolation than if they had acquired smallpox naturally. 

The basis for vaccination began in 1796 when the English doctor Edward Jenner noticed that milkmaids who had gotten cowpox were protected from smallpox. Jenner also knew about variolation and guessed that exposure to cowpox could be used to protect against smallpox. To test his theory, Dr. Jenner took material from a cowpox sore on milkmaid Sarah Nelmes' hand and inoculated it into the arm of James Phipps, the 8-year-old son of Jenner's gardener. Months later, Jenner exposed Phipps several times to variola virus, but Phipps never developed smallpox. More experiments followed, and, in 1801, Jenner published his treatise "On the Origin of the Vaccine Inoculation." In this work, he summarized his discoveries and expressed hope that "the annihilation of the smallpox, the most dreadful scourge of the human species, must be the final result of this practice."