Macrophages are large mononuclear phagocytic cells that play a vital role in the immune response. They are present in all body tissues with extremely heterogeneous and plastic phenotypes that adapt to the organs and tissues in which they live and respond in the first-line against invading microorganisms. Tuberculosis (TB) is caused by the pathogenic bacteria Mycobacterium tuberculosis (Mtb), which is among the top 10 global infectious agents and the leading cause of mortality, ranking above human immunodeficiency virus (HIV), as a single infectious agent. Macrophages, upon Mtb infection, not only phagocytose the bacteria and present the antigens to T-cells, but also react rapidly by developing antimycobacterial immune response depending highly on the production of cytokines. However, Mtb is also capable of intracellular survival in instances of sub-optimal activation of macrophages. Hence, several systems have been established to evaluate the Mtb-macrophage interaction, where the THP-1 monocytes have been developed as an attractive model for in vitro polarized monocyte-derived macrophages. This model is extensively used for Mtb as well as other intracellular bacterial studies. Herein, we have summarized the updated implications of the THP-1 model for TB-related studies and discussed the pros and cons compared to other cell models of TB.