Embryonic stem (ES) cells, isolated from pre-implantation embryos, can grow indefinitely invitro (self-renewal) and have potential to differentiate into all cell types in the body (pluripotency). The nuclear receptor gene family is very important for controlling development, differentiation and homeostasis. Here, we review the new progress in understanding the role of nuclear receptors in ES cells focusing on the structure, expression and function of several nuclear receptors. LRH1, DAX1, Esrrβ and TR2 play critical roles in maintaining pluripotency, while, GCNF, COUP-TFs and sumoylated TR2 are critical in regulating the exit from pluripotency. Nuclear receptors hold great potential as targets of manipulation of ES and iPS cells for applications in regenerative medicine, because they are ligand-activated transcription factors that can be regulated by small molecule agonists and antagonists.