The complex programme of mouse development entails specification of the embryonic epiblast (Epi) as well as of the extra-embryonic trophectoderm (TE) and primitive endoderm (PrE). These three lineages of mouse blastocyst can be modelled in vitro using stem cells derived from primary tissues. In these cultures, cells self-renew while retaining their developmental potential if put back into a developing embryo. Indeed, embryonic stem cells (ESC) when injected into a blastocyst readily contribute to all embryonic lineages. Similarly, trophoblast stem cells (TSC) will give rise to all TE-derived trophoblast lineages and extraembryonic endoderm cells (XEN) will contribute to the PrE-derived yolk sack. These model systems are a powerful tool to study early development, lineage specification and placenta formation. Only recently reproducible and chemically defined culture systems of these cells have been described. This overview discusses such novel methods for culturing ESC/TSC/XEN as well as their molecular signatures and developmental potential. Recent strides in expanding the developmental potential of stem cells as well as achieving models more reminiscent of their in vivo counterparts are discussed. Finally, such in vitro stem cells can self-assemble into structures reminiscent of embryos when used in novel 3D-culture systems. This article discusses the strengths and limitations of such “synthetic embryos” in studying developmental processes.