Embryonic stem (ES) cells — the integrity of which is crucial for embryonic development — are highly sensitive to DNA damage, but the mechanisms underlying rapid death are unclear. Dumitru et al. now show that BAX, a pro-apoptotic member of the B cell lymphoma 2 (BCL-2) family, is maintained in its active form at the trans-Golgi network (TGN) of healthy ES cells and is transferred to mitochondria to induce apoptosis following DNA damage. By contrast, in healthy non-ES cells BAX is only found in the cytosol in an inactive conformation and needs to be both activated and transferred to mitochondria in response to apoptotic stimuli. The authors also show that apoptosis after DNA damage in ES cells depends on p53, which is required for the TGN-to-mitochondria translocation of active BAX. Thus, active BAX at the TGN keeps undifferentiated ES cells primed for rapid death.