The need for an improved vaccine against tuberculosis has never been more urgent. The HIV epidemic and the emergence of multi and extensively drug-resistant strains of Mycobacterium tuberculosis mean that global control of this pathogen remains inadequate. The existing vaccine, BCG, confers only variable protection against pulmonary disease. Exposure to environmental mycobacteria may contribute to this variability in protective efficacy. Protective immunity against Mycobacterium tuberculosis is dependant on a cell-mediated immune response. Boosting BCG with a subunit vaccine, and/or replacing BCG with an improved BCG are both strategies currently being investigated. Since 2002, there have been increasing numbers of TB vaccine candidates entering into clinical trials. The first of these candidates, MVA85A, is safe and highly immunogenic in all trials to date. In addition, the cellular immune response induced is highly polyfunctional. The protective efficacy of MVA85A will be evaluated in a Phase IIb trial commencing in early 2009 in South African infants.