In multicellular organisms, unnecessary or harmful cells, such as those that are cancerous or infected with a virus, are eliminated by apoptosis. After apoptosis, cell corpses are rapidly recognized and phagocytosed by professional phagocytes, such as macrophages and dendritic cells. The rapid removal of cell corpses by phagocytes prevents the release of potentially toxic or immunogenic materials from dying cells. Although a number of molecules on phagocytes have been found to be involved in apoptotic cell clearance in vitro, only a few have been proved to be involved in apoptotic cell clearance in vivo by analyses of knockout animals. These knockout mice commonly suffer from autoimmunity, indicating that the complete removal of apoptotic cells is essential for the maintenance of self-tolerance. In this review, we present an overview of the molecular mechanisms of apoptotic cell clearance by phagocytes and the pathological relevance of the failure of apoptotic cell clearance to autoimmune disorder.