New therapeutics to treat microbial infections are urgently needed to avert the increasing risk of drug resistance. An emerging target with considerable potential for antimicrobial drug development is acetolactate synthase (ALS). This enzyme has previously been successfully used for the commercial development of herbicides. Gene knockout studies of ALS have confirmed it to be an essential enzyme for the survival of mycobacteria and pathogenic fungi in cell culture. Critically, this enzyme is absent in humans, so the need to overcome selectivity is not an issue with this target. The lecture will discuss the advances, and collaborative effort, that has led to further understanding of the molecular structure and function of microbial ALSs, and will also disclose potent inhibitors discovered in the process of rational and irrational design.