As the frontiers of immunological research expand, new insights into the pathogenesis of long poorly understood diseases, such as inflammatory bowel disease (IBD), are opening up new possible avenues for treatment. Myeloid-derived cells (i.e., monocytes, macrophages, neutrophils, and dendritic cells), long believed to be effector cells driving the initiation of inflammation, have been increasingly shown to have immunoregulatory effects previously underappreciated. Dysfunction in the immunoregulatory roles of these cells may play a part in the pathogenesis of a subset of patients with IBD. The role of myeloid-derived suppressor cells, initially described in cancer, have been shown to play an important role in the balancing of effector and regulatory T cells in inflammation as well, and their role in IBD is also explored. The potential for future cell-based therapies for IBD is enhanced by the advances being made in the understanding of the innate immune system in the intestine.