The Cpx and sigmaE signaling systems monitor the cell envelope in Escherichia coli. When induced, each system triggers a signaling cascade that leads to the upregulation of factors needed to combat envelope damage. Although each system is distinct and can be uniquely induced by certain cues, they also share striking similarities. In this review, we discuss the recent progress in our understanding of the Cpx and sigmaE systems and compare how both function to maintain the integrity of the cell envelope.