Recently, important advances have been made in the immunodiagnosis of tuberculosis. New T cell interferon-gamma release assays (TIGRA) are more specific and more sensitive than the tuberculin skin test (TST) for the diagnosis of Mycobacterium tuberculosis (MTB) infection. However, like the TST, TIGRA are unable to distinguish between active tuberculosis (TB), latent TB infection (LTBI) and treated TB if performed on blood mononuclear cells alone. In active TB, MTB-specific T cells are actively recruited to the site of infection and can rapidly be identified in extrasanguinous fluids, such as pleural effusions, ascites, cerebrospinal fluid, and in bronchoalveolar lavages. This review summarizes recent findings comparing systemic and local immune responses against MTB. Although bacteriological and histological methods have the highest specificity for TB in terms of diagnosing active TB and the number of TB patients in whom extrapulmonary TIGRAs have been evaluated is still limited, a comparison of local and systemic MTB-specific immune responses is a promising technique to rapidly distinguish active TB from latent MTB infection in routine clinical practice.