Latent infection with Mycobacterium tuberculosis (LTBI) is defined by the presence of M. tuberculosis-specific immunity in the absence of active tuberculosis. LTBI is detected using interferon-γ release assays (IGRAs) or the tuberculin-skin-test (TST). In clinical practice, IGRAs and the TSTs have failed to distinguish between active tuberculosis and LTBI and their predictive value to identify individuals at risk for the future development of tuberculosis is limited. There is an urgent need to identify biomarkers that improve the clinical performance of current immunodiagnostic methods for tuberculosis prevention, diagnosis and treatment monitoring. Here, we review the landscape of potential alternative biomarkers useful for detection of infection with M. tuberculosis. We describe what individual markers add in terms of specificity for active/latent infection, prediction of progression to active tuberculosis and immunodiagnostic potential in high-risk groups' such as HIV-infected individuals and children.