Smallpox was the first and only disease eradicated worldwide through a global vaccination program. It was caused by the Variola virus. Edward Jenner invented the first vaccine for smallpox using cowpox, a similar but less severe virus, establishing the method of using a weaker strain of a virus to produce vaccines still used today. Containing the disease involved isolating sick individuals at home, an effective approach incorporated into modern infectious disease frameworks. The global smallpox eradication scheme established vaccination as a highly successful public health strategy paving the way for other vaccination programs.