Germ cells undergo epigenome reprogramming for proper development of the next generation. The achievement of in vitro germ cell derivation from human and mouse pluripotent stem cells and further differentiation in a plane culture and in aggregation with gonadal somatic cells offers unprecedented opportunities for investigation of the germ cell development. Moreover, advances in low-input/single-cell genomics have enabled detailed investigation of epigenome dynamics during germ cell development. These technologies have advanced our knowledge of epigenome reprogramming during the specification and development of primordial germ cells, their sex differentiation, and gametogenesis. Key findings include details of chromatin remodeling and transcriptional regulation, progressive and comprehensive DNA demethylation, and tight links between DNA demethylation and histone marks during the development of primordial germ cells, acquisition of unique totipotent epigenome during oogenesis (e.g., broad H3K4me3 domains and low-level three-dimensional genomic organization), and unexpected organization of the sperm genome. Moreover, these studies suggest the importance of epigenome analyses for in-depth evaluations of in vitro gametogenesis.