Mycobacterium tuberculosis causes an infection in humans with clinical manifestations varying from asymptomatic carriage of bacteria to rapidly progressing tuberculosis. Infection outcomes depend on complex and still not fully understood interactions between the pathogenic bacteria and their host organism. Gene expression changes in response to host defense mechanisms are needed for M. tuberculosis survival and functioning. This review focuses on the analysis of dynamic changes in the M. tuberculosis transcriptome taking place during infection processes in host tissues. Presently available data on mycobacterial transcriptome changes obtained from different infection models are discussed. A major part of this review is devoted to the description of biochemical changes occurring in M. tuberculosis infection process, from the primary through latent infection to pathogen reactivation. At each stage of the infection, gene expression changes and induced bacterial metabolic variations are discussed.