A quarter of the world's population is estimated to be infected with Mycobacterium tuberculosis (M.tb) approximately 1.7 billion people. Cell-mediated immunity in the host response to M.tb is of central importance in the diagnosis of M.tb. All the commercially available platforms exploit the fact that M.tb infection, even at very low bacterial burdens as in Latent tuberculosis infection (LTBI), evokes a strong Cell-mediated immunity response to M.tb antigens. LTBI was previously thought to represent a uniform state. However, as research progresses it has become clear that LTBI constitutes a broad spectrum of infection states that differ by the degree of the pathogen replication, host immune response, and inflammation. In parallel with national and international guidelines for TB elimination, awareness, diagnosis, and therefore treatment of LTBI has increased in recent years. Clinical benefits from chemoprophylaxis for LTBI can only occur if IGRA-positive contacts are truly at increased risk of subsequently progressing to active TB compared with IGRA-negative contacts.