Through identification and evaluation of mutations and polymorphisms in components of the IFN gamma response pathways, a better understanding of the mechanisms and risk factors influencing the development of mycobacterial disease is gained. This may lead the way for development of therapeutic and preventative strategies. Although conventional science has focused on identifying discrete mutations, greater awareness of the impact of subtle changes, both at the genetic (polymorphisms) and physical levels (body morphotype), may prove critical in the investigative process. There has been extraordinary progress in the understanding of mycobacterial susceptibility factors over the last few years. The recognition of characteristic phenotypes will lead to the identification of new genetic bases for disease.