The mucosal immune system is governed by a unique set of rules and regulations. The local microenvironment dictates the necessity for these differences. The intestinal epithelial cell (IEC) sits at the interface between an antigen-rich lumen and a lymphocyte-rich lamina propria (LP). The cross talk that occurs between these compartments serves to maintain intestinal homeostasis. IECs have the capacity to talk to LP lymphocytes, activating populations of unique regulatory T cells. These cells have the capacity to talk back to the epithelium, influencing epithelial cell growth and differentiation. This review looks at this cross talk and places it in the context of mucosal immunoregulation.