Antimicrobial resistance to virtually all clinically applied antibiotic classes severely limits the available options to treat bacterial infections. Hence, there is an urgent need to develop and evaluate new antibiotics and targets with resistance-breaking properties. Bacterial cell division has emerged as a new antibiotic target pathway to counteract multidrug-resistant pathogens. New approaches in antibiotic discovery and bacterial cell biology helped to identify compounds that either directly interact with the major cell division protein FtsZ, thereby perturbing the function and dynamics of the cell division machinery, or affect the structural integrity of FtsZ by inducing its degradation. The impressive antimicrobial activities and resistance-breaking properties of certain compounds validate the inhibition of bacterial cell division as a promising strategy for antibiotic intervention.