More than 80 years after the introduction of Bacillus Calmette–GuÉrin, the first tuberculosis vaccine, new vaccines for tuberculosis are finally in clinical trials. The selection of antigens on which new subunit vaccines are based represent the first fulfilment of the promise of proteomics and genomics, and the delivery systems for these antigens are likewise the first fruits of the improved understanding of how the host immune system recognizes pathogens. However, clinical trials are still at Phase I and there remain formidable obstacles to the registration of the first new TB vaccines. Here the authors review the vaccines in clinical trials and discuss the different approaches they take to stimulating immunity to Mycobacterium tuberculosis infection, focusing on recombinant subunit vaccines. The challenges that confront these approaches and how they are being addressed are then discussed.