Summary Immunological studies have supported the idea that innate immunity is critical for the control of Mycobacterium tuberculosis ( Mtb ) infection in humans. Despite the overwhelming evidence showing the critical role of Toll‐like receptors (TLRs) in the in vitro recognition of Mtb , the in vivo significance of individual TLRs has been more difficult to demonstrate consistently. We were interested in examining the role of genes of TLRs and molecules involved in their signalling cascades, and a case–control study was designed to test the association of polymorphisms of these innate immune genes with pulmonary tuberculosis (TB) in a Colombian population. In this study, we did not find an association with TLR2 , TLR4 , TLR9 , MyD88 or MAL/TIRAP polymorphic variants. These findings suggest that those genes are not involved as risk factors for pulmonary TB in our population.