Tuberculosis infection is a serious human health threat and the early 21st century has seen a remarkable increase in global tuberculosis activity. The pathogen responsible for tuberculosis is Mycobacterium tuberculosis, which adopts diverse strategies in order to survive in a variety of host lesions. These survival mechanisms make the pathogen resistant to currently available drugs, a major contributing factor in the failure to control the spread of tuberculosis. Multiple drugs are available for clinical use and several potential compounds are being screened, synthesized, or evaluated in preclinical or clinical studies. Lasting and effective achievements in the development of anti-tuberculosis drugs will depend largely on the proper understanding of the complex interactions between the pathogen and its human host. Ample evidence exists to explain the characteristics of tuberculosis. In this study, we highlighted the challenges for the development of novel drugs with potent bacteriostatic or bactericidal activity, which reduce the minimum time required to cure tuberculosis infection.