The protection afforded by the currently available tuberculosis vaccine, bacillus Calmette-Guérin (BCG) is insufficient and new vaccine strategies are urgently needed. Progress in our understanding of the immunological deficits of BCG combined with novel knowledge on genetics of mycobacteria has paved the way for promising new vaccine strategies. These include recombinant modified BCG vaccines, attenuated strains of Mycobacterium tuberculosis, and various non-live candidates such as DNA and subunit vaccines. Decisive for transforming technical progress into a novel tuberculosis (TB) vaccine strategy is the recent advance in our understanding of the failure of BCG in the third world and the interaction between this vaccine and environmental mycobacteria.