Studies of developmental cell death in the nervous system have revealed two different modes of programmed cell death (PCD). One results from competition for target-derived trophic factors and leads to the stochastic removal of neurons and/or glia. A second, hard-wired form of PCD involves the lineage-specific, stereotypical death of identifiable neurons, glia or undifferentiated cells. Although traditionally associated with invertebrates, this 'programmed PCD' can also occur in vertebrates. Recent studies have shed light on its genetic control and have revealed that activation of the apoptotic machinery can be under the same complex, combinatorial control as the expression of terminal differentiation genes. This review will highlight these findings and will suggest why such complex control evolved.