The role of the intestinal epithelium as part of the physical barrier to infection is well established alongside its central roles in food absorption, sensing nutrients, and water balance. Nematodes are one of the most common types of pathogen to dwell in the intestine. This article reviews recent data that have identified crucial roles for intestinal epithelial cells in sensing these kinds of pathogens and initiating innate responses, which qualitatively influence adaptive immune responses against them. Moreover, it is now clear that the epithelium itself--in addition to the cells that lie within it--are key to many of the protective mechanisms that result in expulsion of these large multicellular parasites from the intestine. An understanding of the IEC and intraepithelial leukocyte response is crucial to both development of mucosal vaccines, and the mechanisms that underlie the emerging use of intestinal dwelling helminths for therapeutic treatments of inflammatory and autoimmune disease.