The preimplantation embryo development leads to the formation of a blastocyst made of two cell lineages: an outer layer of epithelial cells, the trophectoderm, that will give rise to some embryonic annexes, and a mass of undifferentiated cells, the inner cell mass, that will form the foetus and the remaining embryonic annexes. The trophectoderm encloses the inner cell mass and protects it from the external medium. Moreover, after hatching, the trophectoderm invades the uterine tissue, a crucial step for the implantation of the embryo. Therefore, the divergence between these two lineages is of crucial importance for the emergence of the foetus itself and for the postimplantation development to take place correctly. The setting up of cell polarity during compaction at the eight-cell stage allows asymmetric divisions to take place, thereby leading to lineage divergence. Phenotypic properties of these two cell populations are progressively reinforced through cell-cell interactions, outer cells undergoing epithelial differentiation while inner cells remain undifferentiated. Although cellular mechanisms controlling the divergence of the first two lineages are quite well known, important efforts have been carried out this last decade to identify the molecular machinery involved in this process and will be presented in this review.