Francisella tularensis has attracted attention historically as a biological weapon, due to its high infectivity in aerosols, and the severity of disease in humans. There is no licensed vaccine currently available, although an attenuated live vaccine strain (LVS) was identified in the middle of the last century and has been successfully used to protect humans. Efforts are underway to determine the basis of attenuation of LVS, and to understand the immunity required for protection. Alternative approaches to produce subunit vaccines and defined attenuated strains are also in progress. However, the limitations of animal models may make licensing a candidate vaccine challenging.