In humans, Mycobacterium tuberculosis persists for long periods in a clinically latent state, creating a huge reservoir of 'silent' tuberculosis (TB) (roughly one-third of the global population) from which new cases continually arise. A prognostic marker for active TB would enable targeted treatment of the small fraction of infected individuals who are most at risk of developing contagious TB, contributing greatly to TB control efforts. Here, we propose that TB-specific interferon-γ release assays might be useful for identifying individuals with progressive infections who are likely to develop the disease. This might provide an unprecedented advantage for TB control, namely targeted preventive therapy for individuals who are most at risk of developing active contagious TB.