High-grade gliomas represent a formidable challenge to paediatric oncologists. The second most common malignant brain tumour of childhood, little progress has been made in the outcome of these tumours in the last four decades. Outcome remains dire with less than 20% of patients surviving. Current treatment consists of maximal resection and radiotherapy, with chemotherapy both in conjunction with and adjuvant to radiotherapy being added more recently. Yet much of the evidence for the use of chemotherapy is extrapolated from adult data, and evidence for its use in the paediatric population is weak. Recent advances in the biology of high-grade glioma in children identify epigenomic subgroups distinct from those seen in adults, suggesting a separate tumourigenic mechanism and delineating a separate disease entity. The time may be to move forward with a different way of thinking about paediatric tumours. With biological insight comes the promise of more effective therapies, rationally targeted towards the biology of the tumour. This review addresses the current advances in paediatric high-grade glioma and how we can move forward to translate this into improved outcomes for these patients.