Ninety adolescents suffering from tuberculosis with primary drug resistance (PDR) in Mycobacterium tuberculosis (MBT) were followed up. All the patients had active, marked processes, mainly infiltrative tuberculosis in the phase of decay and dissemination. MBT resistance to 3 drugs or more was detected in most patients (62.3%). Multidrug resistance was 32.2%. The course of the disease was chiefly favorable. An exacerbation of the process occurred during therapy in 6.6% of patients. In patients with PDR, abacillation occurred in 100% of cases and the decay cavities closed in 86.6% by the end of the course of therapy. The PDR patients received treatment with both first- and second-line drugs, had surgery, collapsotherapy, laser therapy, and physiotherapeutic treatments, and lidase. Treatment of patients with drug-resistant tuberculosis presents severe difficulties. However, good results can be achieved in most patients, by applying an individual approach to each patient and determining the optimum chemotherapy regimens and pathogenetic treatments.