Resistance to antituberculosis drugs emerged as soon as they were first used. Currently, in France, the main risk factor for resistance remains having previously received antituberculosis drugs. Resistance to isoniazid is 18% in the previously treated population, compared with 5% in the population that has never received antituberculosis drugs. The prevalence of multidrug resistance ranges from 9% to 1%, depending on whether it is measured in a population that has or has not received anti-tuberculosis drugs. Patients who pose management challenges and have a worsened prognosis are primarily those with multidrug resistance, who fortunately account for only about fifty cases per year in France. This resistance can be prevented by adhering to simple management principles, as outlined in this article. If it cannot be prevented, it is essential to diagnose it early using molecular tools. The management of these cases benefits from the expertise of specialized teams in both diagnostic and bacteriological aspects, as well as in treatment. (R.A.)