Embryonic stem cells are able to give rise after differentiation to derivatives of three germinal layers (ectoderm, endoderm, and mesoderm) and to functional gametes. This property of cells is referred to as pluripotency. The pluripotent status of preimplantation embryo cells and embryonic stem cells is maintained by a complicated system of molecular signaling pathways and transcription factors. The key regulators in this system are the transcription factors OCT4 and NANOG. The role and place of these factors in the pluripotency-sustaining system and their interaction with other factors are considered in the review. Data are presented on the structure, chromosomal location, expression, and regulation of the Oct4 and Nanog genes in mammals.