To achieve dosage compensation of X-linked gene expression, female mammalian cells inactivate one X chromosome through a process called X-chromosome inactivation (XCI). A central component of this process is the X-encoded long non-coding RNA Xist. Following upregulation from one X chromosome, Xist spreads in cis, kicking off a plethora of events that ultimately results in stable X-linked gene repression, which is then faithfully transmitted to all daughter cells. In the last decades, intensive work has been undertaken to understand each of the steps in XCI, namely Xist transcription control, Xist spreading and localization, and silencing of gene expression. Recently, several groups have spearheaded the research of Xist's interactome and the factors involved in silencing. Several novel proteins have now been shown to be required for the transcriptional silencing of the X chromosome and/or Xist spreading and localization to the inactive X chromosome. Here, we review these new findings in the context of existing knowledge about Xist-interacting factors.