Approaches to overcome the phenotypic resistance of non-replicating Mtb to most antibiotics by developing new kinds of antimicrobial molecules. We introduced the concept of screening for antimicrobial molecules by testing compounds on bacteria that have been rendered non-replicating by conditions modeling those in the host, including host immune chemistries and metabolic stringencies. We have screened over 1.3 million compounds in such assays. While screening continues, efforts are focused on identifying pathways that the active compounds target. With help from our collaborators, we select for resistant mutants and re-sequence their genomes, test the impact of the compounds on Mtb’s metabolome and use probes based on the compounds to pull down potential targets. Then the fun begins.