Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (M.tb), remains a leading public health problem in most parts of the world. Despite the discovery of the bacilli over 100 years ago, there are still many unanswered questions about the host resistance to TB. Although one third of the world's population is infected with virulent M.tb, no more than 5-10% develop active disease within their lifetime. A lot of studies suggest that host genetic factors determine the outcome of M.tb-host interactions, however, specific genes and polymorphisms that govern the development of TB are not completely understood. Strong evidence exists for genes encoding pattern recognition receptors (TLR, CD14), C-type lectins, cytokines/chemokines and their receptors (IFN-γ, TNF-α, IL-12, IL-10, MCP-1, MMP-1), major histocompatibility complex (MHC) molecules, vitamin D receptor (VDR), and proton-coupled divalent metal ion transporters (SLC11A1). Polymorphisms in these genes have a diverse influence on the susceptibility to or protection against TB among particular families, ethnicities and races. In this paper, we review recent discoveries in genetic studies and correlate these findings with their influence on TB susceptibility.