Drug development for tuberculosis (TB) faces numerous practical obstacles, including the need for combination treatment with at least three drugs, reliance on possibly unrepresentative animal models which may not reproduce key features of human disease and the lack of a well-validated surrogate endpoint for stable cure. Pivotal Phase III trials are large, lengthy and expensive, and the funding and capacity to conduct them are limited worldwide. More rational methods for the selection of priority regimens for Phase III are urgently needed to avoid costly late-stage failures. We examine the suitability of adaptive clinical trial designs for drug development in TB, focusing on designs for Phase IIB and III trials, where we believe the biggest gains in efficiency can be made. Key areas that may be addressed by such designs are improvements in the selection of doses and combinations of drugs in early clinical development and in maximising the power of confirmatory trials in multidrug-resistant TB, where patient numbers and complexity pose practical limitations. We encourage trialists and regulators in this area to consider the advantages that may be offered by these designs and their potential to more effectively and rapidly identify better treatment regimens for TB patients worldwide.