Many and large dumps exist in our knowledge about Mycobacterium tuberculosis infection and disease in infants and children. We still do not understand why some individuals do acquire and others do not acquire the infection in the presence of the same risk factors. We do not understand why some individuals convert from latent to active tuberculosis and why other individuals convert from active to inactive tuberculosis even without treatment. As a matter of fact the immune system mounts a bouncing, robust and polyedral defence against Mycobacterium tuberculosis, but the bacillus is so much artful and dextrous that it has ahead from this immunological fierce accoutrements. Mycobacterium tuberculosis survival, multiplication, and transmission are largely favoured by the immune mechanisms. The granuloma itself is more bacillus- than host-protective. These abilities make Mycobacterium tuberculosis one of more successful human pathogens, but dumps in our knowledge and the counterproductive immunity hinder development of new diagnostics, therapies and vaccines. This occurs in front of an infection which engages one third of the world population and a disease which kills in a year about 1.5 million individuals worldwide. Understanding mechanisms and meaning of immune response in tuberculosis marks out the foundations of strategies with a view to prepare effective vaccines and reliable diagnostic tools as well as to build up therapeutic weapons. To gain these objectives is vital and urgent considering that tuberculosis is a common cause of morbidity and is a leading cause of death.