The last outbreak of smallpox in the United States occurred in 1949, and the last naturally occurring case of smallpox in the world occurred in Somalia in 1977 - 10 years after the World Health Organization started a worldwide campaign to eradicate the disease. Unfortunately, the lingering potential for the use of the smallpox virus in an act of terrorism makes it necessary for healthcare providers to keep current with the prevention, presentation, differential diagnosis, and containment of this serious communicable disease.