Amongst the thirty or so two-component systems known in Escherichia coli, the Cpx system has been described as being a stress response system the main function of which is to respond to damage to the cell envelope via activation of proteases and folding catalysts. Nevertheless, the size of the Cpx regulon (several dozens of target genes) and the diversity of the physiological functions associated with it (resistance to hostile conditions, mobility, adherence factors, metabolism, etc.) indicate that the role of Cpx in cell physiology is undoubtedly more complex. The range of cellular functions affected by activation of the Cpx pathway corresponds quite closely to the description of the physiological state of cells grown in biofilms. We suggest that Cpx is a strategic signaling pathway for facing adverse conditions and for settling biofilm communities. Current knowledge of the regulatory mechanisms of the CpxR response (transcriptional and post-transcriptional) and the interactions between CpxR and the other bacterial regulatory systems are presented.