Investigations into the resistance mechanisms of Firmicutes bacteria against antimicrobial peptides have revealed unique resistance modules comprised of an unusual type of ATP-binding cassette (ABC) transporter, paired with a two-component regulatory system. In these systems, the ABC-transporter is not only involved in detoxification of the peptides, but also in their detection and resulting regulation of gene expression. The manuscript by Hiron et al. (2011) published in this issue describes an intriguing complexity of regulatory circuits and division of labour between the three paralogous modules in Staphylococcus aureus, providing important mechanistic insights and new perspectives for future investigations of these unique systems.