Quorum sensing is one of several mechanisms that bacterial cells use to interact with each other and coordinate certain physiological processes in response to cell density. This mechanism is mediated by extracellular signaling molecules; once a critical threshold concentration has been reached, a target sensor kinase or response regulator is activated (or repressed), facilitating the expression of quorum sensing-dependent genes. Gram-positive bacteria mostly use oligo-peptides as signaling molecules. These cells have a special kind of quorum-sensing systems in which the receptor protein interacts directly with its cognate signaling peptide. The receptors are either Rap phosphatases or transcriptional regulators and integrate the protein family RNPP, from Rap, Npr, PlcR, and PrgX. These quorum-sensing systems control several microbial processes, like sporulation, virulence, biofilm formation, conjugation, and production of extracellular enzymes. Insights of the mechanism of protein-signaling peptide binding as well as the molecular interaction among receptor protein, signaling peptide, and target DNA have changed some earlier perceptions. In spite of the increased knowledge and the potential biotechnological applications of these quorum-sensing systems, few examples on engineering for biotechnological applications have been published. Real applications will arise only when researchers working in applied microbiology and biotechnology are aware of the importance of quorum-sensing systems for health and bioprocess applications.