To date tick-borne flaviviruses causing hemorrhagic fevers in humans have been isolated in Siberia (Omsk hemorrhagic fever virus), India (Kyasanur Forest disease virus), and Saudi Arabia (Akhurma virus). Because of their potential use as biological weapons for bioterrorism, these 3 viruses require level 4 biosafety handling facilities and have been listed as hypervirulent pathogens by the Center for Disease Control and Prevention. Alkhurma virus was isolated in 1995 from patients with hemorrhagic fever in Saudi Arabia. Current evidence suggests that transmission to humans can occur either transcutaneously either by contamination of a skin wound with the blood of an infected vertebrate or bites of an infected tick or orally by drinking unpasteurized contaminated milk. To date a total of 24 symptomatic human cases have been recorded with a mortality rate at 25% (6/24). Pauci-symptomatic or asymptomatic cases are likely but epidemiologic data are currently unavailable. The complete coding sequence of the prototype strain of Alkhurma virus was determined and published in 2001 based on international research project involving investigators from France, Great Britain, and Saudi Arabia. Phylogenetic studies demonstrate that closest known relative of Alkhurma virus is Kyasanur Forest disease virus and that both viruses share a common ancestor. Genetic analysis of several human strains sequentially isolated over a 5-year period showed a very low diversity. This finding has important potential implications for diagnosis and vaccination.