Tuberculosis (TB) remains a large-scale public health problem. Key global priorities for TB care and control include improving case-detection and detecting cases earlier, including cases of smear-negative disease. This document updates existing WHO policy on the use of molecular LPAs for detecting MTBC and resistance to isoniazid and rifampicin directly from sputum specimens and by the indirect testing of MTBC culture isolates. The objectives of this policy guidance are to evaluate the diagnostic accuracy of molecular LPAs for detecting MTBC and rifampicin resistance directly from smear-positive sputum specimens and indirectly from isolates of MTBC, evaluate the diagnostic accuracy of molecular LPAs for detecting MTBC and isoniazid resistance directly from smear-positive sputum specimens and indirectly from isolates of MTBC.