Abstract. Naturally occurring cyclic depsipeptides, microbial secondary metabolites that contain one or more ester bonds in addition to the amide bonds, have emerged as an important source of pharmacologically active compounds or promising lead structures for the development of novel synthetically derived drugs. In particular, their lipidated derivatives have shown the greatest therapeutic potential as antimicrobial agents. Some of those compounds are either already marketed (daptomycin 37) or in advanced stages of clinical development (ramoplanin 32) for the treatment of complicated infections caused by multidrug-resistant bacterial strains. As bacteria progressively become resistant to frontline antimicrobial agents, our capacity to effectively treat bacterial infections becomes severely hindered. Therefore, identifying novel antibacterial targets and new antibacterial chemotherapeutics capable of treating infections from drug-resistant microorganisms is of vital importance.(doi: 10.5562/cca1819)