1. Peter J. Holmberg, MD* 2. Zelalem Temesgen, MD† 3. Ritu Banerjee, MD, PhD‡ 1. *Division of Pediatric Hospital Medicine, Department of General Pediatric and Adolescent Medicine, and 2. †Division of Infectious Disease, Mayo Clinic, Rochester, MN 3. ‡Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN * Abbreviations: BCG: : Bacille Calmette-Guerin CDC: : Centers for Disease Control and Prevention CXR: : chest radiograph DOT: : directly observed therapy EMB: : ethambutol FDA: : Food and Drug Administration HIV: : human immunodeficiency virus IGRA: : interferon-γ release assay INH: : isoniazid LTBI: : latent tuberculosis infection Mtb: : Mycobacterium tuberculosis NTM: : nontuberculous mycobacteria RIF: : rifampin PZA: : pyrazinamide TB: : tuberculosis TST: : tuberculin skin test Although tuberculosis (TB) is an ancient disease, it continues to cause significant morbidity and mortality throughout the world, including among children. Knowledge of appropriate TB screening, diagnostic testing, and treatment recommendations is of vital importance for primary care providers when caring for children at high risk for TB. After completing this article, readers should be able to: 1. Understand the epidemiology of pediatric tuberculosis (TB). 2. Describe the mechanisms of TB acquisition and host response, including T-cell–mediated actions and granuloma formation. 3. Discuss the importance of comorbid conditions, specifically human immunodeficiency virus type 1, on the acquisition and progression of TB disease. 4. Identify risk factors for acquisition of TB infection. 5. Recognize the utility of tests for latent TB infection (LTBI), including the tuberculin skin test, interferon-γ release assays, and the effect of age and Bacille Calmette-Guerin vaccination status on interpretation of results. 6. Define the differences among TB, multidrug-resistant TB, and extensively drug-resistant TB. 7. Understand the principles of therapy and drug regimens for LTBI and TB disease (including drug-resistant TB). One of the most common infectious diseases worldwide, tuberculosis (TB) is estimated to affect almost 1 in 3 individuals across the globe. Despite relatively cheap and accurate diagnostic assays as well as established effective treatment regimens, TB remains a leading cause of death annually. When diagnosed and appropriately treated, TB mortality in children approaches zero. However, with an estimated yearly burden of 1 million new pediatric cases worldwide and most of these remaining undiagnosed, TB continues to pose a substantial threat to global child health. Furthermore, most pediatric infections …