Apoptosis occurs in essentially all tissues as part of development, homeostasis, and pathogenic processes including chronic inflammation and infection. During apoptosis, dying cells can disassemble into smaller membrane-bound vesicles called apoptotic bodies (ApoBDs). Under certain conditions, ApoBDs can mediate intercellular communication by trafficking cellular contents like microRNA to regulate tissue repair. Since billions of cells undergo apoptosis daily, the importance of apoptotic cell disassembly for health and disease is fundamental, yet the mechanisms involved in the generation of ApoBDs as well as their functions are poorly understood. Here, we describe a new mechanism of ApoBD formation via the generation of a novel membrane protrusion called apoptopodia. Mechanistically, we have identified a number of caspase-cleaved proteins such as ROCK1 kinase, PANX1 membrane channels, and Plexin B2 transmembrane receptor as key regulators of ApoBD formation. Functionally, the formation of ApoBDs via apoptopodia could play an important role in cell clearance to limit unwanted inflammation, as well as intercellular communication in the context of viral infection. Additionally, we have also identified a novel selection of FDA-approved drugs that can modulate ApoBD formation. Understanding the mechanistic basis and functional significance of this process will generate fundamental knowledge of the downstream consequence of cell death. Targeting this newly described apoptotic cell disassembly process could be a novel approach for the treatment and management of inflammatory and infectious diseases.