Embryonic stem (ES) cells proliferate indefinitely while maintaining pluripotency. The ability of ES cells to form all cell-types of the embryo can occur because they maintain their genome in an epigenetically-potentiated state that is amenable to a broad series of changes in gene expression. Epigenetic stasis and change occur at a molecular level largely through mechanisms involving chromatin and its modification. This review outlines current knowledge of chromatin homeostasis in undifferentiated ES cells, and the remodeling of chromatin during the course of ES cell differentiation. Furthermore, recent evidence shows that the chromatin of many genes in ES cells is configured in developmentally-potentiated states that index them for later transcriptional outcomes. ES cell chromatin also has dynamic physical and kinetic properties that are probably necessary for rapid and pervasive remodeling upon differentiation. Finally, knowledge of nuclear reprogramming activities in oocytes and ES cells are considered, since these activities may also function in the maintenance of pluripotent ES cell chromatin and are also likely involved in subsequent differentiation.