Tuberculosis is a chronic infection by that results in over 1.5 million deaths worldwide each year. Currently, there is only one vaccine against tuberculosis, the Bacillus Calmette-Guérin (BCG) vaccine. Despite widespread vaccination programmes, over 10 million new infections are diagnosed yearly, with almost half a million cases caused by antibiotic-resistant strains. Novel vaccination strategies concentrate mainly on replacing BCG or boosting its efficacy and depend on animal models that accurately recapitulate the human disease. However, efforts to produce new vaccines against an infection have encountered several challenges, including the complexity of pathogenesis and limited knowledge of the protective immune responses. The preclinical evaluation of novel tuberculosis vaccine candidates is also hampered by the lack of an appropriate animal model that could accurately predict the protective effect of vaccines in humans. Here, we review the role of zebrafish () and other fish models in the development of novel vaccines against tuberculosis and discuss how these models complement the more traditional mammalian models of tuberculosis.© 2020. Published by The Company of Biologists Ltd.