Programmed cell death (PCD) is an important developmental process, but how do cells know when it is time to die? Shai Shaham and co-workers now reveal the role that the transcription factor PAL-1 and the caspase CED-3 play in C. elegans tail-spike cell death(p.1357). Cell death in other C. elegans cells occurs via the EGL-1-mediated inhibition of CED-9, a BCL-2 protein, which triggers the release of the caspase activator CED-4 to cause CED-3 activation and cell death. The researchers show that PAL-1,independently of CED-9 activity, binds to the ced-3 promoter to cause its transcriptional induction. This induction immediately precedes cell death,indicating that ced-3 transcription is the temporal cue for PCD initiation. In pal-1 mutant worms, ced-3 is not upregulated and tail-spike PCD is prevented. Because the mammalian homologue of PAL-1 is Cdx2, which, when mutated, can cause intestinal tumours, the authors propose that by modulating Cdx2 expression, the overproliferation that is associated with intestinal cancers could be targeted.