Unlike Tuberculosis (TB), lung disease is a highly drug-resistant bacterial infection with no reliable treatment options. De novo drug discovery is urgently needed but is hampered by the bacterium's extreme drug resistance profile, leaving the current drug pipeline underpopulated. One proposed strategy to accelerate de novo drug discovery is to prioritize screening of advanced TB-active compounds for anti- activity. This approach would take advantage of the greater chance of homologous drug targets between mycobacterial species, increasing hit rates. Furthermore, the screening of compound series with established structure-activity-relationship, pharmacokinetic, and tolerability properties should fast-track the development of in vitro anti- hits into lead compounds with in vivo efficacy. In this review, we evaluated the effectiveness of this strategy by examining the literature. We found several examples where the screening of advanced TB chemical matter resulted in the identification of anti- compounds with in vivo proof-of-concept, effectively populating the drug pipeline with promising new candidates. These reports validate the screening of advanced TB chemical matter as an effective means of fast-tracking drug discovery.