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Tolerance induction and desensitization in Stevens–Johnson syndrome (SJS) or in toxic epidermal necrolysis (TEN) have been described as an absolute contraindication by some authors, but there are cases where there is no treatment alternative. Tuberculosis (TB) remains a leading cause of morbidity and mortality in developing countries and ranks alongside HIV as a leading cause of death worldwide. Severe drug reactions, such as SJS and TEN, occurring in these individuals are lifethreatening. Since alternative therapies for TB are limited, the role of desensitization and reintroduction becomes essential. We describe a case of tolerance induction to anti-TB drugs in a patient with SJS/TEN overlap syndrome using a specifically designed premedication, comedication, and desensitization protocol.