Glioblastoma multiforme (GBM) is the most common and deadliest cancer of the central nervous system. The existence of stem-like cells within GBM tumors - Glioblastoma stem cells (GSCs) - may explain some of the malignant features of Glioblastoma multiforme (GBM) owing to their rapid self renewal and diffuse migratory behavior. Increasingly apparent is the role ion channels play in many cancer cell properties, including regulation of cell cycle progression and proliferation, tumor cell motility and invasion, and regulation of metabolic rate. We hypothesize that ion channel dysregulation contributes to GSC malignancy, including increased viability, proliferation, and migration. To test this, multiple GSC isolates derived from human GBM tumors were maintained in culture over many passages while retaining stem cell properties. RNA-seq expression profiles revealed ion channel families that were highly enriched in GSC samples. Real-time qPCR was next used to confirm increased expression of voltage gated calcium, sodium, and potassium channels, ionotropic glutamate channels and inwardly-rectifying potassium channels. Identifying ion channels uniquely enriched in GSCs led to functional analyses to determine how ion channel blockers affected their proliferative and migratory properties. We performed MTT cell viability assays to assess how ion channel blockers altered the viability of GSCs compared to a control neural stem cell line. We were able to show a significant decrease in cell viability across GSC lines compared to control at a variety of drug concentrations. Utilizing live-image cell tracking, we determined decreased migratory behavior and rates of these GSC lines with the same blockers. Finally, to elucidate the role of the extrinsic tumour microenvironment on the proliferation and migration of GSCs, unique coculture models involving GSCs cultured on mouse organotypic brain slices were utilized, and showed the affects of stimulating and inhibitory DREADD receptors to modulate local neuronal activity.