Mammalian X-chromosome inactivation is an impressive example of epigenetic gene regulation, whereby the majority of genes on the approximately 160 Mb X chromosome are silenced in a strictly cis-limited fashion. In this review we will discuss the important players involved in the silencing process. The process is initiated by transcription and cis-localization of the non-coding XIST RNA, which then recruits many of the epigenetic features generally associated with heterochromatin, including histone modifications, histone variants and DNA methylation.