Glioblastoma (GBM) is an extremely malignant tumor of the central nervous system, characterized by low response to treatments and reoccurrence. This therapeutic resistance is believed to arise mostly from the presence of a subpopulation of tumorigenic stem cells, known as cancer stem cells (CSCs). In addition, the surrounding microenvironment is known to maintain CSCs, thus supporting tumor development and aggressiveness. This review focuses on a therapeutic strategy involving the stem cell trans-differentiating ability of graphene and its derivatives. Graphene distinguishes itself from other carbon-based nanomaterials due to an array of properties that makes it suitable for many purposes, from bioengineering to biomedical applications. Studies have shown that graphene is able to promote and direct the differentiation of CSCs. In addition, potential usage of graphene in GBM treatment represents a challenge in respect to its administration method. The present review also provides a general outlook of the potential side effects (e.g., cell toxicity) that graphene could have. Overall, this report discusses certain graphene-based therapeutic strategies targeting CSCs, which can be considered as prospective effective GBM treatments.