There is substantial evidence from studies on racial variation in susceptibility to tuberculosis (TB) that human genetic variation is an important determinant of the outcome of infection with Mycobacterium tuberculosis (M tb). In only a minority of cases is there an obvious identifiable risk factor such as human immunodeficiency virus (HIV) infection, advanced age, diabetes, corticosteroid usage or alcohol abuse. In the remainder, a complex interaction of genetic and environmental factors causes the development of clinical TB. Assessment of the contribution of genetics of host resistance to human TB is a long-standing challenge of human genetics research. Several studies demonstrated the association of various human leukocyte antigens (HLA) with disease susceptibility in different ethnic populations. There are likely to be many more TB- susceptibility genes to be identified.