Francisella tularensis is the etiologic agent of tularemia, a severe debilitating disease of humans and animals. The low infectious dose of F. tularensis in humans and the relative ease of culture are probably the properties which originally attracted interest in this bacterium as a bioweapon. Even today, F. tularensis is ranked as one of the pathogens most likely to be used as a biological warfare or bioterrorism agent. A live attenuated vaccine (LVS) has been available for over 50 years, but there are shortcomings associated with its use. This vaccine is not fully licensed and does not offer a high level of protection against respiratory challenge. Nevertheless, this vaccine does demonstrate the feasibility of vaccination against tularemia. Protection against tularemia is likely to be dependent on the induction of cellular and humoral immune responses. These types of responses are induced by the LVS vaccine and could also be induced by a rationally attenuated mutant of F. tularensis. Evoking this range of responses with a sub-unit vaccine may be more difficult to achieve, and will be dependent on the use of suitable vaccine delivery systems.