Cell polarization is critical for lineage segregation and morphogenesis during mammalian embryogenesis. However, the processes and mechanisms that establish cell polarity in the mammalian embryo are not well-understood. Recent studies suggest that unique regulatory mechanisms are deployed by the mouse embryo to establish cell polarization. In this review, we discuss current understanding of cell polarity establishment, focusing on the formation of the apical domain in the mouse embryo. We will also discuss outstanding questions and possible directions for future study.