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Despite the clinical relevance of major tuberculous pathogens to domestic animals and humans, the understanding of mycobacterial transmission modes, pathways, and interactions in their natural habitats remains very limited. The reason for this is primarily because ecological and evolutionary concepts have not yet been widely applied to the understanding of these bacteria. Most existing research on mycobacterial transmission is not founded on hypothesis testing but rather tends to accept the most recent explanation and turn it into a canonical fact. In this comparative review, we discuss plausible alternative hypotheses against a null hypothesis of environmental origin to intensify research on mycobacterial pathogens and their capacity to spread in the context of global change. We highlight a major bias in perceptions of mycobacterial infection transmission, with most work concentrating only on the contagious stage of tuberculous clones. We suggest broadening the field to include research on environmental non-tuberculous mycobacteria and their life histories. A deeper understanding of mycobacterial ecology and evolution is more important now than ever, considering the vast diversity of known and unknown mycobacterial species in natural ecosystems. Infectious disease medicine, veterinary science, and public health surveillance should take a more integrative disease ecology approach to enhance the development of new approaches for control of these animal and human pathogens.