X-chromosome inactivation is a paradigmatic epigenetic phenomenon that results in the mitotically heritable transcriptional inactivation of one X-chromosome in female mammals, thereby equalizing X-linked gene dosage between the sexes. The epigenetic factors and mechanisms that execute X-inactivation overlap with those that regulate embryonic development and disease progression, thus offering a window into the epigenetic processes that regulate development and disease. Here I summarize some recent developments as well as open questions in X-inactivation research. J. Cell. Physiol. 226: 1714–1718, 2011. © 2011 Wiley-Liss, Inc.