To date, tuberculosis (TB) infection, is the most threatening infectious disease in all humans around the world. Mycobacterium tuberculosis is a facultative intracellular bacterium, possesses an exclusive life-cycle inside the macrophages, as one of the most important cells in the innate immune system. As soon as entrance in the lungs, bacteria actively replicate, but intracellular conditions such as hypoxia and nutrient starvation, lead to low replication of bacteria, or nonreplicating state. While Bacillus Calmette-Guerin vaccine is the most usable vaccine, especially in children and against active form, but this vaccine has no more protection in infected adults to latent forms of disease. Among the new generation of vaccines, fusion multistage subunit vaccines have prodigious effect on immune responses. By virtue of simultaneous presence of both expressed antigens from active and latent forms of TB in the structure of these recombinant subunit vaccines, they can strongly induce immune responses against all stages of the disease. The findings suggest subunit vaccines are the best candidates for immunization against TB, by virtue of their high safety, ease of production, specificity, and utilization of mycobacterial immunodominant antigens. Fusion multistage subunit vaccines, as novel subunit vaccines are the most ideal target for proper prevention against TB infection. Due to simultaneous use of both expressed antigens in active and latent forms of TB, these vaccines are able to induce strong immune responses versus all of TB stages.