Apoptosis and the rapid clearance of apoptotic cells (ACs) by professional or nonprofessional phagocytes are normal and coordinated processes that ensure controlled cell growth and stress response with nonpathological outcomes. Uptake of ACs by phagocytes is thought to suppress autoimmune responses through the release of anti-inflammatory cytokines such as interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta), and inhibition of proinflammatory cytokines. The production of pro- and anti-inflammatory cytokines by phagocytes is highly regulated as part of an intrinsic mechanism to prevent inflammatory and autoimmune reactions in a physiological state. Production of IL-10 by phagocytes during clearance of ACs is critical to ensuring cellular homeostasis and suppression of autoimmunity. The molecular mechanism whereby IL-10 production is induced by ACs is only beginning to be understood. This review summarizes our recent work in this aspect of an essential physiological and homeostatic process.