Intestinal mononuclear phagocytes, comprising macrophages (Mφs) and dendritic cells (DCs), play important roles in the generation and the regulation of immune responses to intestinal antigens, and alterations in the development and/or the function of these cells are thought to contribute to the pathogenesis of inflammatory bowel disease. In this review, we discuss the role of tumor necrosis factor-α (TNF) in regulating multiple aspects of intestinal Mφ and DC physiology, including their differentiation, migration, maturation, survival and effector functions. In inflammatory bowel disease, TNF signaling has been implicated in reprogramming monocyte differentiation from the anti-inflammatory Mφ lineage towards the pro-inflammatory mononuclear phagocyte lineage. These cells become a major source of TNF and, thus, may contribute to the chronic inflammatory process. Finally, we highlight some of the important gaps in our current knowledge regarding the role of TNF in Mφ and DC physiology and suggest important directions for future research in this field.