Note that no other type of TA family was identified in _M. tuberculosis_[13, 14]. Most of these systems (63) have been experimentally tested, essentially in _E. coli_ and _M. smegmatis_, for growth inhibition by the putative toxin and its neutralization by the putative antitoxin. Among these, 37 were shown to be functional in at least one of the conditions tested (Figure 1) [15, 16, 17, 18, 19, 20]. This review presents the current knowledge on TA systems in _M. tuberculosis_. Chromosomal map of _M. tuberculosis_ H37 Rv TA systems. TA systems are annotated according to the tuberculist database except for VapBC45 (Rv2018-Rv2019), VapBC49 (Rv3181c-Rv3180c), VapBC50 (Rv3750c-Rv3749c), HigBA2 (Rv2022c-Rv2021c), HigBA3 (Rv3182-Rv3183), YefM/YoeB (Rv3357-Rv3358), and MazEF10 (Rv0298-Rv0299). Most of the TA systems depicted here likely belong to type II, expect for those marked with an asterisk, which are putative type IV systems. For each system, the functionality in _E. coli_ (Ec), _M. smegmatis_ (Msm), and _M. tuberculosis_ (Mtb), is depicted: red color stands for \"inhibition of growth\", grey for \"no inhibition of growth\", and white for \"not tested\". The 10 most induced TA systems in drug-tolerant persister cells are highlighted on dark blue background. The VapBC (_V_irulence associated protein) family of TAs was first discovered as an addiction system of a virulence plasmid of _Salmonella dublin_[21]. They are the most abundant TA loci in _M. tuberculosis_ (Figure 1), defined by a toxin VapC with a PIN domain (homologous to _P_ilT \(\underline{\text{N}}\)-terminal domain) found on proteins from all life kingdoms and generally ribonucleases [22]. Most of the VapC toxins tested so far, including VapC1, VapC2, VapC5, VapC11, VapC20, and VapC29 from _M. tuberculosis,_ exhibit a ribonuclease activity _in vitro_[16, 20, 23, 24]. However, toxicity of the mycobacterial genomes except from _M. marinum_; one GNAT-RHH and one COG5654-Xre were found in _M. gilvum_. VapBC2 [28]. In spite of such differences, the two mycobacterial VapC toxins present a similar putative catalytic site formed by the conserved acidic residues of their PIN domains that coordinate the Mg\({}^{2+}\) ion. In addition, both structures suggest a conserved mechanism of inhibition, in which the VapB antiotoxins prevent efficient binding of Mg\({}^{2+}\) at the active sites of their cognate VapC [23, 28]. The _M. tuberculosis_ VapB antiotoxins are generally related to families of transcriptional regulators or DNA binding domains already reported to be associated with VapC toxins, _i.e._, 33 RHH, 8 Phd, 2 ArbR, and 1 MerR [29]. However, five other VapB do not present any conserved domain. Several VapBC of _M. tuberculosis_ were found to be induced in response to relevant stress conditions encountered during the infection process [16]. This includes hypoxia (VapBC15, VapBC7, and VapBC25) and in IFN- -stimulated murine bone marrow-derived macrophages (VapBC11, VapBC3, and VapBC47). In addition, VapBC3, VapBC31, and VapBC49 were shown to be among the TA systems the most up-regulated in drug-tolerant bacteria, suggesting a possible role in persistence [12]. Interestingly, a recent study in the closely related bacterium _M. smegmatis_ showed that its sole VapC toxin is an RNase that couples the rate of glycerol utilization to bacterial growth via post-transcriptional regulation of genes of sugar transport pathways [30]. In _M. tuberculosis_, it is conceivable that the multiple VapC could act as regulators of translation in response to a plethora of environmental stresses. Intriguingly, the extra cellular concentration of eleven VapC toxins from _M. tuberculosis_, namely VapC4, VapC5, VapC13, VapC19, VapC22, VapC27, VapC37, VapC39, VapC38, VapC41, and VapC44, was increased in a nutrient starvation model, further suggesting a possible role for these toxins during the establishment of latent infection [31]. Overexpression of the _E.