Drug resistant tuberculosis (TB-R), and in particular, multidrug resistant tuberculosis (MDR-TB) is a global public health problem, as well as a problem in our country. Cases of TB-R and MDR-TB have increased mainly in HIV, immigrant and socially disadvantaged populations, but a notable increase in the general population has also been observed. This aspect reinforces the need for a systematic study of sensitivity of all the isolates in a reference laboratory to optimally guide the treatment. Children are especially vulnerable to this severe disease due to the limited knowledge of second line anti-tuberculous drugs, in terms of their pharmacokinetic data, optimal doses, or their long term toxicity, all this eventually resulting in the compassionate use of drugs. Another aspect which further complicates the management of R-TB in children is the limited yield of cultures, which frequently leads to clinician designing drug combinations according to the sensitivity of the initial strain. The epidemiological pattern in our country has currently changed. There is a reported increase in isoniazid-resistant strains; therefore, a four drugs regime is mandatory for the initial period in children, until reliable sensitivity results are available. Treatment should be directly observed or at least supervised by paediatricians. The management of latent infections or exposure to a resistant TB case also requires an accurate, strict and prolonged supervision by expert paediatricians. Authorities and health care professionals who deal with TB should be prepared to face this new phenomenon with appropriate measures. The knowledge of second line drugs for children, as well as mechanisms to ensure the therapeutic adherence and long term control of disease, are essential.