Given that TB still constitutes a tremendous public health problem at the start of the 21st Century, it may come as a surprise that Bacillus Calmette-Guérin (BCG), developed nearly 100 years ago, is today still the only vaccine available against TB. Owing to its limited efficiency in controlling TB, much effort has been deployed to develop new, improved vaccines, with initial preclinical models showing encouraging results. However, since most individuals worldwide have been vaccinated with BCG, new vaccine developments have to be placed in that context. Consequently, several approaches explore the heterologous prime-boost strategy. In this strategy, BCG-primed immunity will be strengthened or prolonged by the administration of antigens present in BCG but formulated in a different manner; either as purified antigens in the presence of appropriate adjuvants, as DNA vaccines or as viral-encoded mycobacterial antigens.