Many factors can influence the dynamic balance that exists between the host and the pathogen (M. tuberculosis), but the host immune response seems to be the most important. This is illustrated by the vulnerability of immune-compromised individuals to develop tuberculosis and by the age-related spectrum of disease witnessed in immune-competent children. This age-related spectrum of disease reflects the ontogeny of the host immune response towards M. tuberculosis. Renewing our focus on the ontogeny of the immune response in children might provide valuable insights to direct future research regarding tuberculosis prevention, vaccine development and treatment.