Cells retain their identity by inheriting gene expression profiles of their predecessors. Patterns of transcription that survive cell division are established and maintained partly through covalent modifications of histones and DNA. Evidence increasingly implicates this epigenetic mode of inheritance in a myriad of developmental processes as well as a cause of or a significant contributor to human disease. We strive to elucidate principles of epigenetic inheritance through the study of X-chromosome inactivation, which is a paragon of epigenetic transcriptional regulation.