Dosage compensation, the mechanism by which organisms equalize the relative gene expression of dimorphic sex chromosomes, requires action of a diverse range of epigenetic mechanisms. The mammalian form, 'named X-chromosome inactivation' (XCI), involves silencing of one X chromosome in the female cell and regulation by genes that make noncoding RNAs (ncRNA). With large-scale genomic and transcriptome studies pointing to a crucial role for noncoding elements in organizing the epigenome, XCI emerges as a major paradigm and a focus of active research worldwide. With more surprising twists, recent advances point to the significance of RNA-directed chromatin change, chromosomal trans-interactions, nuclear organization, and evolutionary change. These findings have impacted our understanding of general gene regulation and are discussed herein.