Synthetic embryology endeavors to use stem cells to recapitulate the first steps of mammalian development that define the body axes and first stages of fate assignment. Well-engineered synthetic systems provide an unparalleled assay to disentangle and quantify the contributions of individual tissues as well as the molecular components driving embryogenesis. Experiments using a mixture of mouse embryonic and extraembryonic stem cell lines show a surprising degree of self-organization akin to certain milestones in the development of intact mouse embryos. To further advance the field and extend the mouse results to human, it is crucial to develop a better control of the assembly process as well as to establish a deeper understanding of the developmental state and potency of cells used in experiments at each step of the process. We review recent advances in the derivation of embryonic and extraembryonic stem cells, and we highlight recent efforts in reconstructing the structural and signaling aspects of embryogenesis in three-dimensional tissue cultures. © 2020 Elsevier Inc.