CD8(+) T cells are activated upon presentation of antigens from the cytosol. Therefore, it was unclear how pathogenic mycobacteria could prime this type of lymphocyte, given that these microbes were thought to remain in phagosomes and, hence, be shielded from the host cytosol. Recently, it was shown that some mycobacteria can enter the cytosol through translocation from phagolysosomes, providing a direct mechanism for CD8(+) T cell priming. However, this mechanism might not apply to other mycobacteria, which do not appear to be able to enter the cytosol. Here, we discuss the different hypotheses to explain the induction of CD8(+) T cell responses in mycobacterial infections.