Early development of the mouse comprises a sequence of cell fate decisions in which cells are guided along a pathway of restricted potential and increasing specialisation. The first choice faced by cells of the embryo is whether to become trophectoderm (TE) or inner cell mass (ICM); TE is an extra-embryonic tissue which will form the embryonic portion of the placenta, whilst ICM gives rise to cells responsible for generating the foetus. In the second cell fate decision, the ICM is further refined into pluripotent cells forming the future body of the embryo, epiblast (EPI) and extra-embryonic primitive endoderm (PE), a tissue essential for patterning the embryo and establishing the developmental circulation. Understanding this early lineage segregation is critical for informing attempts to capture pluripotency and direct cell fate in vitro. Unlike the predictability of nonmammalian cell fate, development of the mouse embryo retains the flexibility to adapt to changing circumstances during development. Here we describe these first cell fate decisions, how they can be biased whilst maintaining flexibility and, finally, some of the molecular circuitry underlying early fate choice.