The pluripotent state of embryonic stem cells (ESCs) provides a unique perspective on regulatory programs that govern self-renewal and differentiation and somatic cell reprogramming. Here, we review the highly connected protein and transcriptional networks that maintain pluripotency and how they are intertwined with factors that affect chromatin structure and function. The complex interrelationships between pluripotency and chromatin factors are illustrated by X chromosome inactivation, regulatory control by noncoding RNAs, and environmental influences on cell states. Manipulation of cell state through the process of transdifferentiation suggests that environmental cues may direct transcriptional programs as cells enter a transiently "plastic" state during reprogramming.