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Glial cells are key drivers of lesion progression in MS with roles in both tissue damage and repair depending on the surrounding microenvironment and the functional state of the individual glial subtype. In this review, we describe recent developments in the context of glial cell diversity in MS summarizing key findings with respect to pathological and maladaptive functions related to disease\u2010associated glial subtypes. A particular focus is on the spatial and temporal dynamics of glial cells including subtypes of microglia, oligodendrocytes, and astrocytes. We contextualize recent high\u2010dimensional findings suggesting that glial cells dynamically change with respect to epigenomic, transcriptomic, and metabolic features across the inflamed rim and during the progression of MS lesions. 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