Contact inhibition of cell proliferation evokes a unique cellular program of growth arrest compared with stress, age, or other physical constraints. The last decade of research on genes activated by cell-cell contact has uncovered features of transmembrane signaling, cytoskeletal reorganization, and transcriptional control that initiate and maintain a quiescent phenotype. This review will focus on mechanisms controlling contact inhibition of cell proliferation, highlighting specific gene expression responses that are activated by cell-cell contact. Although a temporal framework for imposition of these mechanisms has not yet been well described, contact inhibition of cell proliferation clearly requires their coordinated function. Novel targets for intervention in proliferative disorders are emerging from these studies.