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Tuberculosis (TB) is the commonest cause of death by a single infectious agent globally and ranks amongst the top ten causes of global mortality. The incidence of TB is highest in Low‐Middle Income countries (LMICs). Prompt institution of, and compliance with, therapy are cornerstones for a favourable outcome in TB and to mitigate the risk of multiple drug resistant (MDR)‐TB, which is challenging to treat. There is some evidence that adverse drug reactions (ADRs) and hypersensitivity reactions (HSRs) to anti‐TB drugs occur in over 60% and 3%–4% of patients respectively. Both ADRs and HSRs represent significant barriers to treatment adherence and are recognised risk factors for MDR‐TB. HSRs to anti‐TB drugs are usually cutaneous and benign, occur within few weeks after commencement of therapy and are likely to be T‐cell mediated. Severe and systemic T‐cell mediated HSRs and IgE mediated anaphylaxis to anti‐TB drugs are relatively rare, but important to recognise and treat promptly. T‐cell‐mediated HSRs are more frequent amongst patients with co‐existing HIV infection. Some patients develop multiple sensitisation to anti‐TB drugs. Whilst skin tests, patch tests and in vitro diagnostics have been used in the investigation of HSRs to anti‐TB drugs, their predictive value is not established, they are onerous, require specialist input of an allergist and are resource‐dependent. This is compounded by the global, unmet demand for allergy specialists, particularly in low‐income countries (LICs)/LMICs and now the challenging circumstances of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic. This narrative review provides a critical analysis of the limited published evidence on this topic and proposes a cautious and pragmatic approach to optimise and standardise the management of HSRs to anti‐TB drugs. This includes clinical risk stratification and a dual strategy involving sequential re‐challenge and rapid drug desensitisation. Furthermore, a concerted international effort is needed to generate real‐time data on ADRs, HSRs, safety and clinical outcomes of these interventions. [ABSTRACT FROM AUTHOR]