The irrational use of antituberculous drugs led to the emergence of resistant strains of M. tuberculosis. Every year in the world, around 440 000 new tuberculosis cases are due to bacilli that are resistant to the two main antituberculous drugs, isoniazid and rifampicin (also known as multidrug resistant or MDR). Treatment of MDR tuberculosis is difficult and has been based for twenty years on the use of fluoroquinolones and injectable antibiotics such as amikacin, kanamycin and capreomycin. Consequently, strains resistant to the latter drugs, so-called extensively drug resistant strains or XDR, have recently emerged. XDR tuberculosis is very difficult to treat and the prognosis is very close to that of untreated tuberculosis with a mortality rate that can reach 50 % to 100 %. To avoid the emergence of more resistant strains that may lead to almost untreatable disease, we must focus our efforts on the right management of drug susceptible tuberculosis. Basic principles for avoiding accumulation of resistances in selected strains are outlined in the article.