Glial tumours in children have distinct patterns of epigenetic alteration, chromosomal structure, and gene and protein expression that differentiate them from their histological counterparts in adults. Understanding paediatric gliomas at the molecular level provides important prognostic and therapeutic insights, such as which genetic alterations confer a favourable response to adjuvant therapy, or which signalling pathways might be amenable to specific molecularly targeted agents. For clinicians, the ultimate goal is to individualise therapeutic regimens on the basis of the molecular fingerprint of a particular tumour and the prognosis conferred by this profile. In this Review, we examine a series of studies of molecular and genomic analysis of glial tumours in children, and discuss the many clinical insights that these molecular features provide.