Numerous bacterial species inhabit the lumen of the human intestine. The epithelial cells that line the intestinal barrier are in direct contact with many of these species and have developed sophisticated strategies to prevent bacterial invasion of host tissue beyond simply providing a physical blockade. Intestinal epithelial cells (IECs) possess receptors that are capable of recognizing bacterial products, and engagement of these receptors results in the production and secretion of immunoregulatory proteins, such as cytokines and chemokines, which mobilize immune effector cells, including macrophages, dendritic cells, and neutrophils. In addition, IECs can produce various lipid-based eicosanoids that can contribute to the orchestration of the immune response. A better understanding of how the intestinal epithelium interacts with its microbial constituents may provide insight into strategies for treatment of enteric infections and inflammatory bowel disease.