A prerequisite for successful establishment of Mycobacterium tuberculosis in the host is its ability to survive after internalization in alveolar macrophages that they encounter after inhalation. The innate immune response protects some individuals to the extent that they remain uninfected. In others, the innate immune system is not sufficient and an adaptive immune response is generated. This is usually protective, but not sterilizing, and individuals remain latently infected. In susceptible individuals, M. tuberculosis successfully escapes immune surveillance. The interplay between the host innate immune response and the bacterial mechanisms in play to offset this response, is of considerable importance in dictating the course of the disease. In order to gain an understanding of this interplay it is of importance to analyze how M. tuberculosis interacts with innate immune receptors and makes its entry into macrophages, how it subverts the bactericidal effects of macrophages, and dampens processes required for protective immunity, including cytokine and chemokine induction. This review will focus on some of the Indian efforts in these areas, concentrating mainly on the interaction of M. tuberculosis with macrophages and dendritic cells (DCs). The role of the PE/PPE family of proteins in regulating the immune response, will not be discussed in this chapter. The genome-wide approaches of analyzing host-M. tuberculosis interactions will also be discussed elsewhere.