Glioblastoma (GBM) is the most frequent and the most aggressive primary cancer of the brain in adults. Despite aggressive therapeutic interventions, the median overall survival is below 18 months after initial diagnosis. The current standard of care of newly diagnosed GBM includes concurrent administration of temozolomide (TMZ) and radiotherapy followed by adjuvant TMZ. Since 2005, TMZ remained the first-line chemotherapy in treating GBM patients with its ability to cross the blood-brain barrier. However, after initial efficacy, GBM cells acquire resistance to TMZ and other chemotherapeutic agents via multiple mechanisms, including the expression of ATPbinding cassette (ABC) efflux proteins. These transporters are involved in normal physiological functions, i.e., physiological cholesterol transport and elimination of toxins, but also it plays a role in pathological conditions, i.e., chemotherapies drug resistance. In humans, each ABC protein has specific tissue's locations and specific functions. In this review, we highlight the role of ABC proteins superfamily members ABCB1, ABCC1 and ABCG2 in the resistance of GBM cells to chemotherapy.