Gliomas are the most common primary malignancy in human central nervous system. Many similarities in cell morphology and expression of markers exist between cancerous cells and normal undifferentiated progenitor cells. At the molecular level, many important gene products are causally implicated in both the glial differentiation process and glial neoplasm formation. These observations raise the question of to what degree cell differentiation state influences glioma formation. In this review, we discuss new insights into the parallels between glial differentiation and glioma formation as well as the potential application of differentiation-inducing therapy.