The current TB drug pipeline is populated with small molecule drug candidates that act through inhibition of a number of specific protein-based targets. However, the inhibitor-focused drug development approach suffers from several drawbacks, including difficulty in identification of targets amenable to small-molecule disruption, locating druggable sites that adversely impact target activity, and balancing inhibitor potency with potential selectivity and toxicity concerns to establish a therapeutic window. This talk will describe the work of GCADDA4TB, a flagship programme for tuberculosis drug development established as part of the GC ADDA initiative, which is addressing these challenges by pivoting to the development of bacterial proteolysis targeting chimeras (BacPROTACs) as new antituberculosis agents. More specifically, the talk will describe the workflow by which BacPROTACs that target high value proteins of interest (POIs) are developed in a manner that capitalises on our teams’ experience and fulfil various vulnerability and target-assessment criteria. Our most recent successes – and our plans for future studies – will be highlighted to showcase that targeted protein degradation is a viable strategy for anti-tuberculosis drug development.