- The smallpox vaccine is the oldest--and was, for 90 years, the only--vaccine known to man. Many vaccination techniques have been used over time, with no fewer than ten employed during the 20th century alone. In Israel, two main techniques were used prior to smallpox eradication in 1978--multiple punctures using a standard needle, and jet injection--while most other countries adopted the bifurcated needle as the method of choice. Despite the vaccination experience gained over time, doubt remains today as to the preferred vaccination technique. During 2002, when Israel became the first country to conduct large-scale smallpox vaccination in the 21st century, multiple standard needle puncture was adopted as the method of choice, while at the same time the bifurcated needle was readopted in the United States. The article reviews the various smallpox vaccination techniques, the supporting scientific data, and the current lacunae in knowledge related to the subject. Together, these factors will most likely influence the adoption of a preferred vaccination technique during a smallpox emergency.