Tuberculosis (TB) is the biggest killer worldwide of any infectious disease, a situation worsened by the advent of the HIV epidemic and the emergence of multi-drug resistant strains of Mycobacterium tuberculosis. The existing vaccine, Mycobacterium bovis bacille Calmette-Guérin (BCG), has proven inefficient in several recent field trials. There is currently intense research using cutting-edge vaccine technology to combat this ancient disease. However, it is necessary to understand why BCG has failed before we can rationally develop the next generation of vaccines. Several hypotheses that might explain the failure of BCG and the strategies designed to address these shortcomings are discussed.