In spite of successful measures taken to reduce mortality associated with tuberculosis, this disease is still widely spread. In some Russian regions the number of patients with tuberculosis is no short of the epidemic level. The long-term use of antibiotics, changes in the composition of the human microbiota and a few other factors have contributed to the emergence of drug-resistant and hypervirulent sublineages of Mycobacterium tuberculosis. Insufficient fundamental knowledge of mechanisms underlying the emergence and evolution of M. tuberculosis clones simultaneously resistant to a wide spectrum of antibiotics and exhibiting increased virulence complicates the situation and necessitates a new strategy to combat the disease. The key concepts of this strategy are «superorganism», «microbiota» and «resistome». The emergence of multidrug-resistant (MDR) and extensively resistant (XDR) strains should be addressed in the context of the «superorganism»; among its components are the human body, its microbiota (specifically, the bacteria that affect the immune status), and M. tuberculosis itself. Clinically studied phenotypes and genotypes of MDR/XDR strains are a result of clonal variability that M. tuberculosis develops as part of this «superorganism». Therefore, it is important to focus on the development of vaccines, adjuvants and probiotics with selective immunomodulating and antioxidant properties.