Bovine tuberculosis caused by Mycobacterium bovis remains an economically important problem in Great Britain with potential zoonotic consequences, and the incidence is rising exponentially. In 1997 an independent scientific review recommended that the best option for disease control in Great Britain was the development of a cattle vaccine. Bovine tuberculosis remains a significant problem in countries of the developing world. Indeed, more than 94% of the world's population live in countries in which the control of bovine tuberculosis in buffalos or cattle is limited or absent. Effective vaccination strategies would have a major impact in countries that cannot afford expensive test and slaughter-based control strategies. Here, we present a review of progress toward that goal, and discuss how this progress has shaped our research strategy for the development of a vaccine.