There has previously been no robust cell-based model for examining the genetic and epigenetic mechanisms of human germ cell formation. Human embryonic stem cells (hESCs) could potentially fill this need, as all cell types analyzed to date (including mature germ cells) can be identified by marker analysis during hESC differentiation. Furthermore, hESCs could also be used to differentiate mature female germ cells (oocytes) in culture as an alternate reprogramming cell for somatic cell nuclear transfer. However, to differentiate and isolate a functional germ cell from hESCs, the mechanisms that regulate germ cell formation need to be understood. The purpose of this review is to summarize the current understanding of the earliest events in human germ cell formation and to describe some of the known genetic pathways that regulate germ cell specification and development in the mouse. Finally, the current literature on the formation of germ cells from ESCs will be described.