Subfertility affects 1 in 6 couples and despite advances in in vitro fertilization (IVF) and artificial reproduction (ART), the current rate of success remains at ~25%. As infertility is often unexplainable, there is increasing need for better knowledge of the molecular and cellular processes that control human preimplantation development (the first 7 days following fertilization) to understand and treat the underlying causes. Further, the advent of cell reprogramming has dramatically accelerated the hopes for future regenerative medicine, and also highlighted the need for better understanding of how pluripotency and lineage specification are regulated during human pre-implantation development. During this window of development, the zygote (1 cell) undergoes a series of cell divisions and cellular differentiation to acquire distinct gene expression profiles and cellular fates2–8, ultimately establishing the first lineages: 1) trophectoderm (TE; prospective placenta), 2) primitive endoderm (PE; prospective yolk sac), and 3) pluripotent epiblast cells (EPI; prospective embryo proper)2. Remodelling of global transcriptional and translational landscapes, signal transduction, clearing of maternal mRNA and epigenetic reprogramming are all involved in the regulation of this complex and coordinated process, however, the precise mechanism(s) underlying lineage segregation or cell cycle in the human embryo remains to be determined. The majority of what we know about preimplantation development has been extrapolated from studies using the mouse, and while the mouse has provided a wealth of information, with recent advancements in technology it is apparent that striking species differences exist; as such, not all prior knowledge on preimplantation development can be effectively translated to the human developmental biology; highlighting the need for detailed cross-species studies to determine the suitability of such models. With recent advancements in single-cell genomics, we can now successfully measure the molecular content in an individual cell – a technology that is optimal for studying the molecular biology in the developing embryo.