The uptake of apoptotic cells by macrophages and dendritic cells or nonprofessional phagocytes is crucial for development and tissue homeostasis. This is of special importance because deficiencies in the recognition or removal of apoptotic cells may result in autoimmune diseases. The efficient elimination of an apoptotic cell involves contact between the altered cell and the phagocyte, specific recognition, and phagocytosis of the target. These processes are closely associated with the release of anti-inflammatory cytokines and the induction of self-tolerance. This review focuses on the different types of signals, bridging molecules and receptors involved in both steps of the uptake process. Additionally, the role of soluble pattern recognition molecules from the innate immune system, known for a long time to discriminate pathogens from self and more recently to sense altered self, is discussed. This applies to complement Clq, which appears to sense multiple ligands exposed at the apoptotic cell surface, to be involved in their engulfment by phagocytes, and to modulate dendritic cell maturation.