Diagnosing latent tuberculosis (TB) infection (LTBI) is important globally for TB prevention. LTBI diagnosis requires a positive test for infection and negative evaluation for active disease. Current tests measure an immunologic response and include the tuberculin skin test (TST) and interferon-gamma release assays (IGRAs), T-SPOT.TB and QuantiFERON. The IGRAs are preferred in bacille Calmette-Guérin–vaccinated populations. The TST is still used when cost or logistical advantages over the IGRAs exist. Both TST and IGRAs have low positive predictive values. Tests that differentiate the TB spectrum and better predict future TB risk are needed.