Recent developments have shown that inappropriate activation of apoptotic pathways contributes to many neurodegenerative diseases. The basic mechanisms that underlie apoptosis in neurodegenerative diseases are uncertain, although they likely represent the subversion of normal developmental programs. Several types of neuronal cell death have been reported, including autophagic and caspase-independent cell death. In this review we consider evidence for the participation of apoptotic caspases in neuronal development, and examine the hypothesis that differentiating neurons undergo stage-specific alterations in apoptosis sensitivity that may be due to caspase regulation. In addition, we present data supporting this hypothesis.