Isoniazid (H) is one of the most important first-line medicines for the treatment of active tuberculosis (TB) and latent TB infection (LTBI), with high bactericidal activity and a good safety profile. The emergence of TB strains resistant to isoniazid threaten to reduce the effectiveness of TB treatment. About 8% of TB patients worldwide are estimated to have rifampicinsusceptible, isoniazid-resistant TB (Hr-TB). In April 2017, the World Health Organization (WHO) convened a Guideline Development Group (GDG) meeting to develop policy guidelines on the treatment of Hr-TB. The development of these policy guidelines was conducted in accordance with procedures established by the WHO Guideline Review Committee. This was the first time that Hr-TB treatment recommendations were developed following the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) to review the evidence and formulate the recommendations. This method included an assessment of the quality of the evidence, a consideration of the overall balance of benefits and harms (at individual and population levels), health equity, resource use, acceptability and feasibility of interventions across a variety of settings, including those where access to drug-susceptibility testing (DST) is limited. The new recommendations for the treatment of Hr-TB complement the 2016 update of the WHO treatment guidelines for DR-TB. The recommendations will also feature in a chapter of the forthcoming update of the Companion Handbook to the WHO guidelines for the programmatic management of drug-resistant TB and replace previous recommendations for the treatment of Hr-TB based on expert opinion.