Initiation of X-inactivation is known to depend on the presence of a unique region or locus known as the X-inactivation center, or Xic, defined by the study of chromosomal rearrangements. Its mode of action is currently unknown but is the scene of much research effort. This review explores the recent literature concerning the definition of Xic and its relationship both to Xist and to another genetic entity thought to play a role in the initiation of X-inactivation, the X-controlling element, or Xce.