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Tuberculosis caused by Mycobacterium (M.) tuberculosis remains a global public health threat. Over the last few decades, antitubercular research mainly focused on mechanisms of identifying by which activated macrophages can slaughter or the proliferation of M. tuberculosis bacilli prevented in a cell-dependent manner. In this regard, for disease resolution, inflammatory cytokines are very crucial. Here, we demonstrate how macrophages act as the first line of defense against the M. tuberculosis. Studies have revealed a dual role in M. tuberculosis infection played by macrophages. It is worth mentioning that the macrophages are the crucial immune effector and antigen-presenting cells that play the anti-tubercular response, which is the habitat of M. tuberculosis, hence, followed by progressing the disease protecting M. tuberculosis. This dual role can be correlated with the different macrophage polarization statuses, namely, M1 and M2. Herein, we have stated how the several polarization conditions of macrophages are directly linked to the immune responses during host and M. tuberculosis pathogen interactions. We have proposed that macrophage polarization and repolarization are of paramount significance for the anti-tubercular immune response that may involve a sterile cure of the disease. This article summarizes the immune response to M. tuberculosis, the polarization states of macrophages during M. tuberculosis and the repolarization of macrophages by some agents during some diseases including M. tuberculosis, which may be an important factor in the World Health Organization’s target to cure tuberculosis by 2035.