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During development and throughout life, a variety of specialized cells must be generated to ensure the proper function of each tissue and organ. Chromatin plays a key role in determining cellular state, whether totipotent, pluripotent, multipotent, or differentiated. We highlight chromatin dynamics involved in the generation of pluripotent stem cells as well as their influence on cell fate decision and reprogramming. We focus on the capacity of histone variants, chaperones, modifications, and heterochromatin factors to influence cell identity and its plasticity. Recent technological advances have provided tools to elucidate the underlying chromatin dynamics for a better understanding of normal development and pathological conditions, with avenues for potential therapeutic application.