Embryonic stem cells (ESCs) have the potential to differentiate into cells of all tissue types, as demonstrated by their capability to contribute to the development of all germ layers in chimeras and to form teratomas. Of interest, however, is the lack of evidence of gametogenic gonadal tissues within teratomas, such as testicular tubules or follicles. Although this may reflect the fact that in vivo germ cell development and subsequent gametogenesis are complex biological processes, the generation of putative primordial germ cells (PGCs) has been reported during the differentiation of mouse and human ESCs in in vitro systems. In addition, mouse ESCs can even lead to the development of putative gametes, but the efficiency of this process needs to be improved and the functionality of the gametes remains to be proven. Interest in the generation of fully functional gametes from ESCs lies in an experimental model fundamental to the study of reproductive biology, a potential unlimited source of oocytes as a reprogramming bioreactor, and perhaps even in therapeutic applications to overcome human reproductive problems.