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Background: On the basis of recent clinical trial data for the treatment of drug-susceptible and drug-resistant tuberculosis (TB), the American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America have updated clinical practice guidelines for TB treatment in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. Methods: A Joint Panel representing multiple interdisciplinary perspectives convened with American Thoracic Society methodologists to review evidence and make recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) and GRADE-ADOLOPMENT (adoption, adaptation, and, as needed, de novo development of recommendations) methodology. Results: New drug-susceptible TB recommendations include the use of a novel 4-month regimen for people with pulmonary TB and a shortened 4-month regimen for children with nonsevere TB. Drug-resistant TB recommendation updates include the use of novel regimens containing bedaquiline, pretomanid, and linezolid with or without moxifloxacin. Conclusions: All-oral, shorter treatment regimens for TB are now recommended for use in eligible individuals.