Here we discuss the application of the zebrafish as a relatively new model host for the study of mycobacterial pathogenesis. Recent advances in our understanding of host-mycobacteria interactions from the zebrafish include insights into the role of the innate immune system in both controlling and facilitating infection. Analysis in the zebrafish has revealed that innate macrophages restrict initial bacterial growth, but also convey infecting bacteria into the granuloma, which serves as a place for bacterial growth and spread. Bacterial virulence determinants interact with these processes at different steps in pathogenesis, which can be dissected in these living see-through hosts. As these studies uncover new facets of the bacteria-host interactions in tuberculosis they raise even more questions for future investigation.