The flavoenzyme DprEl catalyses a crucial step in arabinan production for cell wall biosynthesis in Mycobacterium tuberculosis and is a highly vulnerable drug target. It was first discovered using benzothiazinones (BTZ): exquisitely potent bactericidal agents that are being developed as drugs to treat tuberculosis. Subsequently, many compounds with diverse scaffolds were found to act as either covalent or noncovalent DprEl inhibitors. Covalent inhibitors, like the BTZ, are all nitroaromatic compounds that serve as suicide substrates after DprEl-mediated nitroreduction. Here, we describe how high resolution structures of DprEl, alone and in complex with various ligands, explain enzyme activity and inhibition.