During early development, embryonic cells can form derivatives of all three embryonic layers. This pluripotency, which is regulated by a gene regulatory network that includes the transcription factors Oct4 and Nanog, is lost in mouse embryos between about E7.5 and E8.5. Here (p. 2288), Rodrigo Osorno, Anestis Tsakiridis and colleagues investigate the precise timing and mechanism of pluripotency loss in the mouse embryo. Pluripotency, they report, is extinguished at the onset of somitogenesis, and the loss of pluripotency coincides with reduced chromatin accessibility of the regulatory regions of Oct4 and Nanog, and decreased expression of these genes. Notably, pluripotency correlates with threshold levels of Oct4 and, consistent with this observation, the researchers identify a novel non-pluripotent state during which an increase in Oct4 expression can rapidly reverse chromatin closure and restore pluripotency. Finally, the researchers show that this temporary state is followed by permanent methylation-based epigenetic stabilization of the non-pluripotent state. Thus, two mechanistically separate events are responsible for the elimination of pluripotent cells during development.