The transcription factor Oct‐4 is expressed specifically in the totipotent germline cycle of mice. Cells that lose Oct‐4 differentiate along different paths to form embryonic and extraembryonic somatic tissue. Oct‐4 may maintain the potency of stem and germline cells by preventing all other differentiation pathways. Oct‐4 may also regulate the molecular differentiation of cells in the germ lineage as it progresses from the fertilized egg, through cleavage stage/morula blastomeres, blastocyst, inner cell mass, epiblast, germ cells, and gametes. The factors that regulate, and are regulated by, Oct‐4 are reviewed with respect to the phenomena of cell potency and germ/soma segregation and differentiation. BioEssays 20:722–732, 1998. © 1998 John Wiley & Sons, Inc.