X-chromosome inactivation (XCI) is an epigenetic phenomenon that equalizes the number of X-linked gene products between male and female eutherian mammals by inactivating one of the two X chromosomes. XCI is essential for female mammalian development, and its failure can lead to embryonic death in mutant mice. The pattern of which X chromosome is inactivated changes dynamically during mouse embryogenesis, depending on developmental stages and tissues. Recent progress in molecular biology, including next-generation sequencing (NGS)-based analyses, enables the analysis of gene expression profiles at a single cell level. Combined with NGS technology, live imaging systems can now be used to track epigenetic events and clarify their casual and spatiotemporal relationships to cell differentiation and embryonic development. Here, I describe a novel live-cell imaging system based on “Momiji” mice for monitoring XCI at the single cell level.