Macrophages are professional scavengers of apoptotic and necrotic cells, and hence constantly take up self antigens. Paradoxically, macrophages are also professional antigen-presenting cells, which would seem to invite autoimmune disorders. Moreover, macrophages are effector cells in the tissue-destruction phase of autoimmune disorders, where they encounter additional self antigens in the stimulatory context of chronic inflammation. This review examines the array of immunosuppressive mechanisms which may help macrophages suppress unwanted T cell responses, and considers the consequences of a breakdown in these negative-regulatory systems in autoimmunity.