Tularemia remains an important zoonosis as well as primary pathogen of wild and domestic animals. It is caused by a small, aerobic, facultatively intracellular, Gram-negative coccobacillus, Francisella tularensis. The species consists of four recognized subspecies: F. tularensis subsp. tularensis (formerly type A), F. tularensis subsp. holarctica (formerly type B), F. tularensis subsp. mediasiatica and F. tularensis subsp. novicida. Although the organism is pathogenic to 190 animal species, clinical cases are associated mainly with lagomorphs and rodents. Tularemia can take multiple clinical forms depending on the portal of entry. It is plague-like and for humans the infectious dose is very low. The natural reservoirs are mice, muskrats, water rats, ground squirrels, voles and rabbits. In humans infection by F. tularensis occurs primarily after inadvertent exposure to infected wildlife species, most frequently rodents, hares, and rabbits. Transmission to animals and humans occurs through arthropod or insect vectors, via direct contact, by ingestion or by inhalation of aerosolized organisms. F. tularensis invades macrophages and spreads to regional lymph nodes causing inflammatory lesions resembling buboes encountered in plague. The organism disseminates throughout the body to the internal organs, reaching lungs, spleen, liver and kidneys. At the final, sepsis stage, the secretory changes develop, taking ulceroglandular form of tularemia. In sheep clinical signs include fever, rigid gait, diarrhea, frequent urination, weight loss, and difficulty breathing. In humans the ulceroglandular tularemia is the most common form of disease and usually occurs following a tick or deer fly bite or after handling of an infected animal. The most serious form is pulmonary and typhoid form of tularemia. Oropharyngeal form results from eating or drinking contaminated food or water. PCR, RT-PCR, a specific fluorescent antibody test or immunohistochemistry are safe and convenient methods for detection and identification of F. tularensis in clinical specimens. Serological tests (slide agglutination test, tube agglutination test, microagglutination test and ELISA), are useful for diagnosing human infection, but are of limited value in the more susceptible animal species that usually die before developing antibodies. The organism is considered as a serious potential bioterrorist threat and is classified as Category A select agent.