Tuberculosis (TB) vaccine research has reached a unique point in time. Breakthrough findings in both the basic immunology of Mycobacterium tuberculosis infection and the clinical development of TB vaccines suggest, for the first time since the discovery of the Mycobacterium bovis bacillus Calmette–Guérin (BCG) vaccine more than a century ago, that a novel, efficacious TB vaccine is imminent. Here, we review recent data in the light of our current understanding of the immunology of TB infection and discuss the identification of biomarkers for vaccine efficacy and the next steps in the quest for an efficacious vaccine that can control the global TB epidemic.