Diagnosis of latent tuberculosis infection (LTBI) should be targeted toward individuals and groups with high risk of progression to active tuberculosis (TB). Low-risk populations should not be screened. Interferon-gamma release assays (IGRAs) perform as well or better than the tuberculin skin test in most targeted populations. IGRAs are preferred for bacille Calmette-Guérin (BCG)-vaccinated populations. A positive IGRA in a person at low risk for TB exposure should be confirmed with a repeat test or another method before recommending LTBI treatment. The choice of which IGRA to use is generally based on the costs and feasibility of performing the test.