What causes Drosophila larval neuroblasts to self-renew with each round of cell division? Insights into this are not only of interest to neurobiologists but also to stem cell researchers. Polycomb group (PcG) genes in mammals are known to regulate stem cell fate and proliferation. Now on p. 1091 of this issue,Bello et al. show that mutations in five of the Drosophila PcG genes increase the expression of the posterior Hox genes abd-A and Abd-B and subsequently induce neuroblast death. This phenotype is rescued by blocking apoptosis. The segmental determination and lineage, but not cell death, of abdominal secondary neuroblasts relies on posterior Hox gene expression. Thus, PcG genes regulate neurogenesis differently in varying developmental contexts. The contributions that other known PcG target genes,such as cell cycle regulators, make in this setting remain to be determined. Individual PcG genes regulate different processes both in mammals and flies;however, the deregulation of Hox gene expression is a common feature of PcG mutants.