In this chapter, host immune response against M. tuberculosis and its role in susceptibility to TB, the importance of non-genetic factors influencing the incidence of TB are explained. Genetic susceptibility to TB is dealt with detailed account of immune response genes, biological functions of human leucocyte antigen (HLA) are covered. HLA and disease association are then explained in detail. This chapter also exhaustively covers immunogenetics of TB including population and family studies and role of non-HLA antigen genes. Further, candidate genes in TB, key aspects of innate immunity to TB and the role of toll-like receptors are discussed.