Metalloenzymes represent and important, but underdeveloped, class of therapeutic targets. Metalloenzyme inhibitors are in clinical use for a wide range of illnesses, from viral diseases such as HIV/AIDS and influenza, to systematic diseases including hypertension and cancer. However, despite these important advancements, the vast majority of metalloenzyme targets remain undrugged. In this presentation, efforts to develop metalloenzyme Fragment-Based Drug Discovery (mFBDD) as a means to improve hit-to-lead efforts for these targets are described. Specifically, recent advances in the use and characterization of metal-binding isosteres (MBIs),[1-3] the development of new fragments,[4] and even the use of mFBDD for developing chimeric molecules for targeted protein degradation (TBD) will be discussed.[5]