The precise determination of when and where cells undergo programmed cell death is critical for normal development and tissue homeostasis. Cao et al. (2007; see p. 843 of this issue) report that the Fork head (Fkh) transcription factor, which is essential for the early development and function of the larval salivary glands in Drosophila melanogaster, also contributes to its demise. These authors show that fkh expression in the salivary glands is normally lost at puparium formation, which is approximately 12 h before they undergo massive cell death triggered by the steroid hormone ecdysone, making room for their developing adult counterparts. The loss of Fkh eliminates its role in blocking cell death, allowing for subsequent ecdysone-induced reaper and head involution defective death activator expression and tissue destruction. This study provides new insights into the transcriptional regulation of programmed cell death and the mechanisms that underlie the precise spatial and temporal control of hormone responses during development.