Currently no effective therapies are available for glioblastoma. Florio and colleagues identified, via computational screening, triamterene as a CLIC1 blocker that suppresses human glioblastoma stem cell proliferation, invasiveness, and tumor growth. Triamterene also enhances temozolomide and radio-chemotherapy efficacy, making it a repurposed therapeutic candidate for glioblastoma treatment in future clinical applications.