Antibiotic resistance is only set to increase if significant action is not taken to combat the imminent threat of multidrug resistant pathogens. The development of inhibitors of the enzyme dihydrodipicolinate synthase (DHDPS), which is involved in the diaminopimelate pathway, represents an attractive approach to the discovery of new antibacterial agents. Herein, the challenges and opportunities of DHDPS inhibitors are discussed.