The staphylococcal agr locus encodes a quorum sensing (QS) system that controls the expression of virulence and other accessory genes by a classical two-component signaling module. Like QS modalities ill other Gram-positive bacteria, agr encodes all autoactivating peptide (AIP) that is the inducing ligand for AgrC, the agr signal receptor. Unlike other such systems, agr variants have arisen that show strong cross-inhibition in heterologous combinations, with important evolutionary implications. Also unlike other systems, the effector of global gene regulation in the agr-system is a major regulatory RNA, RNAIII. In this review, we describe the functions of the agr system's elements, show how they interact to bring about the regulatory response, and discuss the role of QS in staphylococcal pathobiology. We conclude with the suggestion that agr autoactivation, unlike classical enzyme induction, call occur under suboptimal conditions and call distinguish self from non-self by inducing ail exclusive and coordinated population wide response.