Pulmonary tuberculosis, a disease caused by infection M. tuberculosis, is a main infectious disease of death in the world. Even though the developed countries are combating the infection successfully, in undeveloped parts of the world infection is spreading uncontrollably. M.tuberculosis is evolving strong mechanisms of resistance and virulence. In the 20th century pulmonary tuberculosis has changed its clinical presentation because of the earlier recognition of the disease and more effective treatment. It seemed that the infective agent is under control and the number of contaminated is falling, but new challenges emerged. The emergence of HIV-infection, prolonged life expectancy of patients with chronic diseases and more aggressive therapeutic options have favoured the emergence of new groups of patients at increased risk of contracting TB. The risk of pulmonary infection is higher with the patients who have HIV infection than the ones who do not have. The coinfection of M. tuberculosis with HIV accelerates the replication of the virus and the progression of the disease because of the lower immunity of the body cells which is caused by HIV infection. The research and the clinical experience have confirmed the connection between the pulmonary tuberculosis infection and the use of biological therapy, especially TNF-α blockers infliximab, adalimumab and etanercept. Also, one of the main challenges of tuberculosis treatment is the appearance of pharmacoresistant types which do not respond to standard therapeutic antituberculotic protocols. Treatment regime of those types demands long term therapy with new drug types. Development of molecular biology and genetic research is a man's attempt to be one step in front of Mycobacterium, to evolve diagnostical procedures of high sensitivity and specificity, to recognise the infection on time and efficiently treat it. BCG vaccination is a procedure done in Croatia continually with the goal of tuberculosis infection prevention, and the result is that the infection is now successfully under control and almost eradicated. The fact that magnifies the importance of tuberculosis infection in the eyes of public health is that under the lead of World Health Organization a new strategy of tuberculosis infection prevention was launched and its' goal is to lower the number of new patients by 90% until 2035. as opposed to 2015.