The genetic analysis of susceptibility to infections has proven to be extremely useful for identification of key cells, molecules, pathways, and genes involved in the battle between two genomes – the essence of the infectious process. This is particularly true for tuberculosis and other mycobacterial infections which traditionally attracted much attention from both immunologists and geneticists. In this short review, we observe results of genetic studies performed in human populations and in animal models and compare relative input of forward and reverse genetic approaches in our knowledge about genetic control of and immune responses to mycobacterial infections.