###### Abstract  
The World Health Organization (WHO) End Tuberculosis (TB) Strategy has set ambitious targets to reduce 2015 TB incidence and deaths by 80% and 90%, respectively, by the year 2030. Given the current rate of TB incidence decline (about 2% per year annually), reaching these targets will require new transformational tools and innovative ways to deliver them. In addition to improved tests for early and rapid detection of TB and universal drug-susceptibility testing, as well as novel vaccines for improved prevention, better, safer, shorter and more efficacious treatments for all forms of TB are needed. Only a handful of new drugs are currently in phase II or III clinical trials, and a few combination regimens are being tested, mainly for drug-resistant TB. In this article, capitalising on an increasingly rich medicine pipeline and taking advantage of new methodological designs with great potential, the main areas where progress is needed for a transformational improvement of treatment of all forms of TB are described.  
tuberculosis treatment; biomarkers; drug combination; clinical trial 2020_00 10, 2605; doi:10.3390/app10072605  
On 14 May 2014, the 67 th World Health Assembly (WHA) endorsed a resolution detailing the global strategy to control and eliminate tuberculosis (TB) in the 2015-2030 Sustainable Development Goal (SDG) era [1]. The 3-pillar strategy was branded as the \"End TB Strategy\" [2]. Additional to two pillars devoted to patient-centred care and to health system policies, a third pillar is fully devoted to research and the need of innovations. This pillar and its components are fundamental in reaching ambitious international targets set as part of the new strategy to \"End TB\": to reduce 2015 TB incidence and deaths by 80% and 90%, respectively, by the year 2030. The simple projection model underpinning such figures, presented at the 67 th WHA, is based on previous empirical experiences showing the plausibility of declining trends conducive to those targets. The large-scale interventions promoted by the End TB Strategy would be able to reduce TB incidence at a much higher annual rate than the current 1.5-2% per year [3]. For instance, it is known that in the Netherlands, United Kingdom, Germany and other western European countries, TB incidence was declining at 8%-10% per year during the late 1950s and 1960s thanks to wide access to diagnosis and effective chemotherapy, screening of people at risk, affordable care and social protection mechanisms [4]. It is also known that additional intensive interventions, including large-scale preventive therapy, were associated with even faster declines reaching 17% per year among the small Inuit populations of Alaska and North-Western Territory of Canada [5]. However, while these declines could in theory be achieved with optimal implementation of existing diagnostic and treatment tools--which are better than those available 70 years ago--the needed acceleration towards 15%-20% incidence decline per year to reach the 2030 targets will require new transformational tools and innovative ways to deliver them. These tools need to cover all aspects of TB care and its cascade, as well as prevention.