Embryonic stem cells (ESCs) have a remarkable capacity for pluripotency; that is, they are capable of differentiating into all types of cell lineages. Recent studies have reported that successful differentiation of mouse ESCs into primordial germ cells (PGCs) as well as into mature male and female gametes can be achieved in vitro and in vivo. In addition, human ESCs can be differentiated into PGCs. The differentiation of ESCs into germ cells of various stages appears to be a spontaneous and quick process, probably due to the nature of ESCs themselves and the microenvironment of the culture conditions that favor this process. Although the functionality of these ESC-derived gametes remains to be established, derivation of both male and female gametes from ESCs raises the possibility of using these gametes to gain a better understanding of basic reproductive biology and, in particular, in conjunction with nuclear transfer technology, to extend the potential for therapeutic cloning and the treatment for infertility. We review the current knowledge on the potential of ESCs to differentiate into both male and female gametes.