Some species of the Mycobacterium tuberculosis complex (MTBC), particularly Mycobacterium tuberculosis that causes human tuberculosis (TB), are the first cause of death linked to a single pathogen worldwide. In the last decades, evolutionary studies have much improved our knowledge on MTBC history and have highlighted its long co-evolution with humans. Its ability to remain latent in humans, the extraordinary proportion of asymptomatic carriers (1/3 of the entire human population), the deadly epidemics and the observed increasing level of resistance to antibiotics are proofs of its evolutionary success. Many MTBC molecular signatures show that these bacteria are not only a model of adaptation to humans, but that they have also influenced human evolution. Due to the unbalance between the number of asymptomatic carriers and the number of patients with active TB, some authors suggest that infection by MTBC could have a protective role against active TB disease and also against other pathologies. However, it would be inappropriate to consider these infectious pathogens as commensals or symbionts, given the level of morbidity and mortality caused by TB.