Edited by Wilhelm JustNervous system development is a process that integrates cell proliferation, differentiation, and programmed cell death (PCD). PCD is an evolutionary conserved mechanism and a fundamental developmental process by which the final cell number in a nervous system is established. In vertebrates and invertebrates, PCD can be determined intrinsically by cell lineage and age, as well as extrinsically by nutritional, metabolic, and hormonal states. Drosophila has been an instrumental model for understanding how this mechanism is regulated. We review the role of PCD in Drosophila central nervous system development from neural progenitors to neurons, its molecular mechanism and function, how it is regulated and implemented, and how it ultimately shapes the fly central nervous system from the embryo to the adult. Finally, we discuss ideas that emerged while integrating this information.Keywords: apoptosis; Drosophila; neurodevelopment Apoptosis shapes Drosophila neural development from the emergence of neuroectoderm in the embryo to the eclosing adult. The earliest indication of programmed cell death (PCD) during neurodevelopment is at embryonic stages 11-12 [1-3], when the first neurons and epidermal cells die [4,5]. Neuronal apoptosis then increases dramatically peaking at embryonic stages 16-17, when the ventral nerve cord (VNC) condenses [3] and the embryo produces its first twitching movements [1]. Although the observed amount of neuronal death differs from embryo to embryo [5], symmetry in neuronal PCD is often observed between the right and left sides of a single embryo [1], indicating that both deterministic and 'random' processes participate in the selection of surviving neurons.Programmed cell death in Drosophila neural development comes in different flavors. It can be triggered by spatial, temporal, nutritional, hormonal, and metabolic signals; it can be regulated by Hox genes, Notch, and other signaling pathways; it can be mediated by one or more proapoptotic genes; and it can act at the stage of neural precursors, of newly born or of mature neurons/glia. What is clear is that dying is not trivial for a cell. Many layers of regulation exist that ensure