The complement system is regarded as an ancient host defense mechanism that helps to promote phagocytosis and/or killing of foreign microorganisms. Less well known is the facilitatory role that complement and other closely related molecules of the innate immune system play in the removal of dying cells. In this chapter, we review the complement system and the mechanisms of complement activation that include natural antibodies and acute phase proteins. The effects of spontaneous and genetically engineered mutations on function of these proteins and their relationship to autoimmune diseases such as lupus are discussed. We also review the known function of non-complement receptors and their roles in recognition and removal of dying cells in normal cellular homeostasis and in inflammation.