In animals, programmed cell death (PCD) is a universal feature of development and is critical for adaptive responses during cellular injury. In both vertebrates and invertebrates, dying cells often progress through a series of ultrastructural changes referred to as apoptosis. This form of PCD involves condensation of nuclear material and fragmentation into “apoptotic bodies” that are eventually engulfed by phagocytes. It is well established that apoptosis requires genetic functions within the dying cell and that the underlying molecular machinery is evolutionarily conserved. Studies in model systems have elaborated common control points in pathways that regulate cell death. However, when considered within larger networks of interactions, the importance of these regulatory “linchpins” can vary across different cell types and across different species. Here, we consider these similarities and differences and discuss how the Drosophila model organism may shed light on evolutionary pressures that fundamentally shaped this biological process.