During central nervous system development, excessive numbers of neurons are initially generated, before approximately half of them undergo programmed cell death (PCD), often during synapse formation. The factors that regulate central neuron survival and synaptic specificity remain largely unknown, but now,Joshua Sanes and colleagues (see p. 4141) report that the protocadherin-γ (Pcdh-γ) gene cluster, which encodes a family of 22 adhesion molecules, is important for the survival of developing neurons, but not for the specificity of their synaptic connections. By selectively inactivating the Pcdh-γ cluster in the mouse retina, the authors demonstrate that the PCD of certain retinal cell types is accentuated by the loss of γ-Pcdhs, whereas the formation of appropriate synapses and of complex functional circuits remains unaffected. Importantly,these findings suggest that γ-Pcdh-mediated regulation of neuronal survival is independent of synaptic connectivity. These results are complemented by a study on p. 4153 by Joshua Weiner and co-workers, who report that γ-Pcdhs promote the survival of mouse spinal interneurons in a non-cell-autonomous fashion.