The epithelium of the gastrointestinal tract is the interface between luminal contents and the mucosal immune system. It must function as a selective barrier to limit penetration of antigens yet keep the mucosal immune system "informed" for the purpose of generating oral tolerance responses to food antigens or commensal organisms and host defense responses against pathogens. Alterations in epithelial barrier function have been proposed to play a significant role in gastrointestinal disease. In this review, we will discuss mechanisms of regulation of epithelial barrier function, and we will focus on the emerging understanding of how secreted immunoglobulins play a role in antigen-specific antigen sampling across the gastrointestinal epithelium.