Germline and somatic stem cells are distinct types of stem cells that are dedicated to reproduction and somatic tissue regeneration, respectively. Germline stem cells (GSCs), which can self-renew and generate gametes, are unique stem cells in that they are solely dedicated to transmit genetic information from generation to generation. We developed a strategy for the establishment of germline stem cell lines from embryonic stem cells (ES). These cells are able to undergo meiosis, generate haploid male gametes in vitro and are functional, as shown by fertilization after intra-cytoplasmic injection into mouse oocytes. In other approach, we show that bone marrow stem (BMS) cells are able to trans-differentiate into male germ cells. BMS cell-derived germ cells expressed the known molecular markers of primordial germ cells. The ability to derive male germ cells from ES and BMS cells reveals novel aspects of germ cell development and opens the possibilities for use of these cells in reproductive medicine. Conversely, we showed that adult male germline stem cells, spermatogonial stem cells (SSCs), can be converted into embryonic stem cell like cells which can differentiate into the somatic stem cells of three germ layers. Understanding how SSC can give rise to pluripotent stem cells and how somatic stem cells differentiate into germ cells could give significant insights into the regulation of developmental totipotency as well as having important implications for male fertility and regenerative medicine.