The worldwide eradication of smallpox, a major achievement in public health, is currently threatened by the risk of bioterrorism. The debate on the destruction of the Variola virus in the two reference laboratories of the World Health Organization has dramatically switched to the preservation of the remaining virus after the September 2001 terrorist events in the U.S. along with the intentional release of Bacillus anthracis in the U.S. The risk of intentional release of Variola virus

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... a minimal, yet possible risk. A smallpox epidemic could have a devastating impact due to its elevated morbidity and mortality that would inflict in non-immune human population, in addition to the ensuing panic and social unrest. Therefore, the development of national preparedness and response plans along with the availability of smallpox vaccine to be used in the post-exposure phase represent a fundamental part of the preventive efforts to cope with bioterrorism. Reestablishing a preventive vaccination program was recently recommended by the Advisory Committee on Immunization Practices (ACIP). However, the vaccine currently available has historically been associated with serious adverse reactions, even death. Thus, this recommendation has not been universally accepted. To counter an epidemic of smallpox, medical personnel in the frontline need to be prepared with updated smallpox information to identify, diagnose, isolate, and treat cases if a bioterrorist attack should occur. Herein we present an indepth review for health care personnel with relevant epidemiologic, clinical, and preventive information on smallpox.