Rifampicin remains the backbone of curative short-course therapy for drug-susceptible tuberculosis, yet the same property that makes it indispensable as an antimycobacterial, sustained activation of the pregnane X receptor, makes it the most consequential enzyme inducer in routine clinical use. Full induction of hepatic and intestinal cytochrome P450 enzymes and of P-glycoprotein develops over roughly a week and dissipates over about two weeks after the drug is stopped, so the interaction burden is present for the entire six-month regimen and for a transitional fortnight on either side of it. This review sets out the molecular basis of that induction, then works through the drug classes where the clinical stakes are highest: antiretrovirals, oral anticoagulants, hormonal contraceptives, calcineurin inhibitors in transplant recipients, oral antidiabetic agents, statins, and the newer anti-tuberculosis agents used in drug-resistant disease. For each class the question is not whether an interaction exists but what to do about it, and the available answers fall into a small set of recurring strategies: substitute rifabutin where its weaker induction is tolerable, escalate the dose of the victim drug under measured monitoring, switch to a method or molecule that does not depend on the induced pathway, or defer a non-essential drug until induction has resolved. The final section translates these strategies into decision support suited to settings that carry most of the world's tuberculosis and the least laboratory capacity, where therapeutic drug monitoring is scarce and the prescriber at the point of care is often not the one who started the interacting drug. The weight of evidence supports a structured, anticipatory approach built around the induction time course rather than reactive dose chasing.