X-chromosome inactivation (XCI) is a crucial mechanism of dosage compensation in female mammals ensuring that genes from only one X chromosome are expressed, initiated through expression of the long noncoding RNA Xist. Recent evidence underscores the significance of molecular crowding-most likely via liquid-liquid phase separation (LLPS)-in forming Xist RNA-driven condensates critical for establishing and sustaining the silenced state. By integrating existing knowledge and emerging ideas, we provide a comprehensive perspective on the molecular underpinnings of XCI and outline how manipulation of LLPS-based mechanisms offers new avenues for novel therapeutic approaches.