With more than 1.3 million deaths annually in the world, tuberculosis (TB) remains as the leading cause of death by a single infectious agent and one of the most important causes of mortality in adults infected with human immunodeficiency virus (HIV). Although efficient chemotherapy is available, TB treatment is long and based in several antibiotics, which results in poor compliance, failure of the treatment, toxicity and emergence of drug-resistant strains. Mycobacterium tuberculosis (Mtb) can produce progressive disease or latent infection. In high endemic areas, infection first occurs in childhood and in most cases is controlled. Only 10% of these primary infections lead to progressive disease. Certain human polymorphisms and several experimental models of pulmonary TB, have demonstrated the necessary activation of T helper cell type 1 and correct expression of cytokines such as interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-12 for the containment of the infection or absence of susceptibility of Mtb infection. Immune response against Mtb infection remains as the cornerstone of the pathogenesis of TB.