Tularemia, caused by the Gram-negative bacterium Francisella tularensis, can be contracted by the bite of an arthropod vector or by inhalation. This disease occurs relatively infrequently but can be severe and even life-threatening if untreated. Until recently, there were few laboratories studying this organism; however, concerns over its potential use as a biological weapon have led to renewed attention to F. tularensis research, particularly in the area of vaccine development. Advances in the ability to genetically manipulate F. tularensis, along with knowledge gained from the creation and refinement of attenuated bacterial vaccines for other diseases, continue to foster significant progress in the development of live-attenuated bacterial vaccines, as well as defined antigen and subunit vaccines.