Host genetic factors play a major role in determining differential susceptibility to major infectious diseases of humans. Infectious diseases in humans appear highly polygenic with many loci implicated but only a minority of these convincingly replicated. Over the course of time, humans have been exposed to organisms like "Mycobacterium tuberculosis". It is possible that the human genome has evolved in part from our exposure to "M. tuberculosis". Animal model studies and whole genome screens can be used to identify potential regions on a gene that suggest evidence of tuberculosis susceptibility. In the case of "M. tuberculosis," animal model studies were used to suggest evidence of a locus which was correlated with susceptibility, further studies were done to prove the link between the suggested locus and susceptibility. The genetic loci that have been identified as associated with susceptibility to tuberculosis are HLA-DR, INF-γ, SLC11A1, "VDR", MAL/TIRAP, and CCL2. Further studies will be needed to determine genetic susceptibility to other infectious diseases and ways public health officials can prevent and test for these infections to enhance the concept of personalized medicine.