Human primordial germ cells (hPGCs), the precursors of sperm and oocytes, arise from the early post-implantation embryo. Nascent hPGCs migrate to the developing gonads, where they undergo meiosis and differentiate into gametes. Fertilization of the oocyte by the sperm results in a totipotent zygote that gives rise to all cell lineages, including the germline itself. Thus, germ cells provide an enduring link between all generations and specification of hPGCs is the critical first step in the germline cycle. The inaccessibility of early post-implantation human embryos represents a challenge to understand the mechanisms of hPGC formation (Tang et al, Nature Review Genetics 2016). To circumvent this obstacle, we developed robust and tractable in vitro methods to reconstitute hPGC specification from pluripotent stem cells (Irie et al, Cell 2015; Kobayashi et al, Nature 2017). Using cutting-edge genomic and epigenomic technologies, we found that SOX17 is the critical transcription factor for hPGC fate. SOX17 cooperates with other co-factors, including its downstream target PRDM1, to activate germ cell genes, repress somatic genes and initiate a unique epigenetic reprogramming process. Detailed epigenomic analysis on hPGCs isolated from embryonic gonads revealed that hPGCs undergo comprehensive DNA demethylation; coupled with genome-wide chromatin reorganization (Tang et al, Cell, 2015). These global epigenetic changes facilitate gametogenesis and ensure that germ cells carry the appropriate epigenomic information for the next generation. Overall, these findings have paved the way for in vitro gametogenesis and have wide-ranging implications for reproductive health, epigenetic inheritance and origins of germ cell cancer.