The pattern of receptors sensing pathogens onto host cells is a key factor that can determine the outcome of the infection. This is particularly true when such receptors belong to the family of pattern recognition receptors involved in immunity. Mycobacterium tuberculosis, the etiologic agent of tuberculosis interacts with a wide range of pattern-recognition receptors present on phagocytes and belonging to the Toll-like, Nod-like, scavenger and C-type lectin receptor families. A complex scenario where those receptors can establish cross-talks in recognizing pathogens or microbial determinants including mycobacterial components in different spatial and temporal context starts to emerge as a key event in the outcome of the immune response, and thus, the control of the infection. In this review, we will focus our attention on the family of calcium-dependent carbohydrate receptors, the C-type lectin receptors, that is of growing importance in the context of microbial infections. Members of this family appear to be key innate immune receptors of mycobacteria, capable of cross-talk with other pattern recognition receptors to induce or modulate the inflammatory context upon mycobacterial infection.