Human germline is a new research frontier and except for the gene regulatory network that governs the specification of this lineage at around 3^rd week of gestation, nothing much is known about it especially because the ethical constraints and technical challenges associated to the access of the human primordial germ cells that undergoes most extra-ordinary epigenetic reprogramming which is characterized by acutely hypomethylated whereby DNA methylation is virtually wiped out, besides loss of other epigenetic constraints. Such establishment of epigenetic ground state is not only critical for human germ cells to initiate meiosis and gametogenesis but also for the establishment of totipotency and subsequent development to term. On the other hand, the genes encompassing the a handful of loci that exhibits resistance to this onslaught of global epigenetic resetting serves as the only candidates of transgenerational/​intergenerational epigenetic inheritance in human. While in-vitro gametogenesis has been possible in case of rodents, our understanding about meiotic entry and formation of gametes in primates remains obscure as all the efforts to recreate gametes from in-vitro-derived primordial germ cells of primates, including that of human, have failed thus far.