Francisella tularensis (F. tularensis) is one of the most infectious pathogens known. Although the disease caused by this bacterium is rarely fatal with appropriate antibiotic therapy, it is often severely debilitating. Laboratory work with F. tularensis poses a significant hazard, and it is essential that appropriate laboratory facilities, trained personnel, and suitable working practices are in place in any organization working with this pathogen. Work with human virulent strains should be carried out at containment level 3. Vaccines play an important potential role in the protection of individuals working with F. tularensis, but the live vaccine strain (LVS) vaccine is not currently licensed for use in humans. Because antibiotic therapy is central to the treatment of human tularemia, antibiotic resistance markers for use in genetic manipulation studies should be carefully selected.