Epithelial cells line the gastrointestinal (GI) mucosa and form an important barrier that protects the subepithelial tissue against a wide array of noxious substances, allergens, viruses, and luminal microbial pathogens. Restoration of mucosal integrity following injury requires epithelial cell decisions that regulate signaling networks controlling gene expression, survival, migration, and proliferation. Over the past few years, polyamines have been shown to play a critical role in GI mucosal repair, and the control of cellular polyamines is a central convergence point for the multiple signaling pathways. Both the function of polyamines in rapid intestinal mucosal epithelial restitution and the underlying mechanism, especially the implication of K(+) channel activity, are the subject of this mini-review article.