Primordial germ cells, which carry the responsibility for perpetuation of the species, are set aside from their somatic neighbors very early in mammalian embryonic development. The founder population of germ cells is rare and difficult to identify and isolate in quantities suitable for molecular and biochemical analysis, thereby highlighting the importance of an in vitro system for deriving germ cells from embryonic stem cells. This chapter details methods for in vitro derivation of germ lineage elements and discusses potential applications of these techniques in germ cell research.