Currently, intercellular chemical signaling in bacteria, known as quorum sensing, is described for several species of bacteria; however, for many clinically important pathogens this significant sensory mechanism remains unknown. Among such pathogens are the pyogenic streptococci that include groups A and B streptococcus (GAS, GBS). Evidence now points to a family of transcription factors, known as Rgg/GadR/MutR, can serve as receptors for secreted pheromones. Within the genome of Streptococcus pyogenes four Rgg paralogs can be identified, two of which (Rgg2 and Rgg3) were shown to rely on short hydrophobic peptides (SHPs) to control transcription of their target promoters. SHPs were found to promote biofilm development and could offset biofilm-dispersion effects caused by Rgg1. Since Rgg homologs are present in genomes throughout Firmicute species, their newfound ability to serve as quorum-sensing mediators offers a potential opportunity to manipulate bacterial behaviors by interfering with communication networks.