A new efficacious tuberculosis (TB) vaccine has the potential to dramatically assist control efforts for the global TB epidemic. Good progress has been made with the clinical development of new TB vaccine candidates with twelve being actively tested in clinical trials. However, there are challenges that would need to be addressed before a new vaccine is licensed for public use. The diversity of risk in populations would need to be factored into clinical development plans. Specific but feasible clinical endpoints need to be agreed upon. TB vaccines would need to be efficacious in both uninfected and infected populations. An achievable efficacy target needs to be set. Standardisation of trial outcomes and the development pipeline would need to be brought about. Alternative routes of administration should be thoroughly explored. There should be sufficient adequately prepared trial sites for doing TB vaccine assessments. Creative use of study designs should be used to expedite progress towards licensure but at the same time containing costs. There should be sufficient funding to support the TB vaccine development. These challenges can be met through commitment by role-players within the TB vaccine arena and with support by external stakeholders.