X chromosome inactivation represents a paradigm for monoallelic gene expression and epigenetic regulation in mammals. Since its discovery over half a century ago, the pathways involved in the establishment of X-chromosomal silencing, assembly, and maintenance of the heterochromatic state have been the subjects of intensive research. In placental mammals, it is becoming clear that X inactivation involves an interplay between noncoding transcripts such as Xist, chromatin modifiers, and factors involved in nuclear organization. Together these result in a changed chromatin structure and in the spatial reorganization of the X chromosome. Exciting new work is starting to uncover the factors involved in some of these changes. Recent studies have also revealed surprising diversity in the kinetics and extent of gene silencing across the X chromosome, as well as in the mechanisms of XCI between mammals.