High-grade gliomas (HGGs) are aggressive brain tumours associated with poor prognosis and treatment outcomes. Novel therapeutic strategies are urgently needed to improve patient outcomes. One approach currently under investigation is targeting the subventricular zone (SVZ), a specialized region of neural stem and progenitor cells in the adult brain. This review explores the role of the SVZ in gliomagenesis and examines preclinical and clinical studies investigating the effects of SVZ irradiation in HGGs. The potential mechanisms underlying the efficacy of SVZ irradiation are discussed, and the clinical relevance of SVZ in HGGs is highlighted. Retrospective studies examining the relationship between SVZ irradiation and survival metrics have yielded mixed results, with some studies favouring targeting the SVZ and others not. Prospective studies have also shown conflicting findings. The debate over whether to irradiate or spare the SVZ continues, considering the potential impact on cognitive function and survival outcomes. This review provides insights into the current understanding of the SVZ as a potential therapeutic target in HGGs and outlines future directions for research and clinical translation.