X chromosome inactivation achieves dosage equivalence for most X-linked genes between the two X chromosomes in females and the single X chromosome in males. In this article the evidence for random inactivation of an X chromosome is reviewed, along with the exceptions that result in nonrandom inactivation. Another exception to X chromosome inactivation is the presence of genes that escape inactivation and are expressed from both the active and inactive X chromosomes. The phenotypic consequences of such expression from the inactive X chromosome are discussed. The major players in the process of inactivation are presented. Initiation of inactivation requires the functional RNA, XIST, and the subsequent stable inactivation of the X chromosome relies upon the recruitment of many other factors, the majority of which are generally associated with heterochromatin.