Dendritic cells and macrophages play an essential role in immune homeostasis in the intestine. They have the critical task of maintaining the balance between tolerance to the intestinal microflora and potential food antigens while retaining the ability to initiate immunity against pathogens. For patients with Crohn's Disease, the tolerance/immunity balance is disturbed and these individuals suffer from chronic intestinal inflammation driven by aberrant T cell reactivity to intestinal bacteria. As antigen presenting cells are required for T cell activation, intestinal phagocytes with the capacity to present antigens from intestinal bacteria to T cells are likely involved in initiating and propagating Crohn's Disease. Recent data describe unique subsets of human intestinal phagocytes that may be involved in the aberrant reactivity to commensal flora that drives Crohn's Disease pathogenesis. This review summarizes the current knowledge of phagocyte subsets in the intestine and mesenteric lymph nodes in healthy individuals and Crohn's Disease patients. Deciphering the function of intestinal phagocytes in health and disease is crucial to advance our understanding of the cellular mechanisms underlying this debilitating disease, provides a potential way to improve treatment for patients with inflammatory bowel disease.