Tuberculosis (TB) is an important cause of morbidity and mortality worldwide. The World Health Organization (WHO) has implemented and scaled-up three important global public health strategies (i.e., DOTS, Stop TB, and End TB) to improve the international scenario. Their epidemiological impact was relevant, as they decreased the number of potential new cases of disease and death. However, the emergence and spread of TB/HIV coinfection and multidrug-resistant TB have hindered the progress towards the elimination of TB by 2050. More efforts are required to increase the global annual decline of the TB incidence rate. Political commitment is necessary, with global and national strategies oriented to the adoption and adaptation of the international, evidence-based recommendations on diagnosis, treatment, and prevention. Research and development activities should be planned to improve the current tools adopted to fight the disease. New rapid diagnostics, an updated and effective therapeutic armamentarium, and an effective preventive vaccine could represent the solution to address the current epidemiological threats.