Mononuclear phagocytes are vital for control of inflammatory responses. Mononuclear phagocytes are highly adaptable effector cells that engage in diverse, often antagonistic processes: DC and macrophages are capable of both stimulating or suppressing T cell-mediated responses depending upon their state of activation. Under normal physiological, noninflammatory conditions, immature DC and macrophages present self and innocuous antigens to T cells in a subimmunogenic context. Recognition of cognate antigen in the absence of costimulation causes effector T cells to die, become anergic, or convert into regulatory T cells. Thereby, antigen presentation by nonactivated mononuclear phagocytes contributes to the steady-state maintenance of self-tolerance. A second “class” of myeloid regulatory cell arises as a consequence of persistent stimulation with proinflammatory mediators. Such activation-induced myeloid suppressor cells presumably serve as counterregulators that limit self-injurious inflammatory responses. Activation-induced myeloid regulatory cells are phenotypically diverse and operate through a variety of mechanisms, including production of T cell-suppressive soluble factors, receptor-mediated killing of effector T cells, and the activation-dependent induction of Tregs.