This Perspective summarizes recent developments in our understanding of the signaling pathways involved in the regulation of epithelial cell adhesion in the gut. The role of phosphatidylinositol 3-kinase signaling in the modulation of adherens junctions, and the connections between tight junctions and nuclear transcription factors, are discussed. The effect of gastrins on adherens and tight junctions is presented as an example of the regulation of adhesion by growth factors. The consequences of dysregulation of adherens junctions and tight junctions for human pathology are also considered.