Phagocytic clearance of apoptotic cells is an important physiologic homeostatic mechanism that is associated with non-inflammatory or anti-inflammatory sequalae. Disruption of the process of apoptotic cell clearance may contribute to development of a number of inflammatory and autoimmune diseases. In this review, we summarize the molecular pathways that have been suggested to account for phagocytic clearance of apoptotic cells. We discuss potential mechanisms for regulation of phagocytosis and the implications for development of autoimmunity.