Resistance of bacterial pathogens to current antibiotics has grown to be an urgent crisis. Approaches to overcome this challenge include identification of novel targets for discovery of new antibiotics. Bacterial topoisomerase I is present in all bacterial pathogens as a potential target for bactericidal topoisomerase poison inhibitors. Recent efforts have identified inhibitors of bacterial topoisomerase I with antibacterial activity. Additional research on the mode of action and binding site of these inhibitors would provide further validation of the target and establish that bacterial topoisomerase I is druggable. Bacterial topoisomerase I is a potentially high value target for discovery of new antibiotics. Demonstration of topoisomerase I as the cellular target of an antibacterial compound would provide proof-of-concept validation.