Apoptosis ensures quick death and quiet clearance of unwanted or damaged cells, without inducing much, if any, immunological responses from the organism. In metazoan organisms, apoptotic cells are swiftly engulfed by other cells. The degradation of cellular content is initiated in apoptotic cells and completed within engulfing cells. In apoptotic cells, caspase-mediated proteolysis cleaves protein substrates into fragments; nuclear DNA is partially degraded into nucleosomal units; and autophagy potentially contributes to apoptotic cell removal. In engulfing cells, specific signaling pathways promote the sequential fusion of intracellular vesicles with phagosomes and lead to the complete degradation of apoptotic cells in an acidic environment. Phagocytic receptors that initiate the engulfment of apoptotic cells play an additional and crucial role in initiating phagosome maturation through activating these signaling pathways. Here we highlight recent discoveries made in invertebrate models and mammalian systems, focusing on the molecular mechanisms that regulate the efficient degradation of apoptotic cells.