Display omitted •SoxE proteins influence many aspects of nervous system development.•SoxE proteins interact cell- and stage-specifically with transcription factors.•SoxE proteins recruit chromatin modifiers and accessory transcriptional machinery.•SoxE proteins regulate microRNA expression.•SoxE proteins establish multiple regulatory feedforward and feedback loops. Sox8, Sox9 and Sox10 represent the three vertebrate members of the SoxE subclass of high-mobility-group domain containing Sox transcription factors. They play important roles in the peripheral and central nervous systems as regulators of stemness, specification, survival, lineage progression, glial differentiation and homeostasis. Functions are frequently overlapping, but sometimes antagonistic. SoxE proteins dynamically interact with transcriptional regulators, chromatin changing complexes and components of the transcriptional machinery. By establishing regulatory circuits with other transcription factors and microRNAs, SoxE proteins perform divergent functions in several cell lineages of the vertebrate nervous system, and at different developmental stages in the same cell lineage. The underlying molecular mechanisms are the topic of this review.