Neuro-oncology is currently in the midst of a paradigm shift in terms of our accepted understanding of the pathophysiology of gliomagenesis. Classic "dedifferentiation" hypotheses, modeling the cellular origin of gliomas after neoplastic transformation of differentiated glia, are currently being challenged by hypotheses suggesting dysregulated glial progenitor cells are responsible for gliomagenesis. Growing evidence exists that glial progenitor cells persisting in the adult mammalian brain, lining the lateral ventricles in the subventricular zone (SVZ) and dentate gyrus, play a role in gliomagenesis. Gliomas frequently occur in close proximity to the ventricular system and SVZ with high-grade lesions like GBM "spreading" to midline structures and crossing the corpus callosum to the contralateral hemisphere. Glial progenitor cells lining the lateral ventricles in the SVZ and dentate gyrus may be the source of "tumor" cells "spreading" to midline structures such as the corpus callosum as well as continuously replenishing the tumor bed resulting in local recurrences.