Glioblastoma multiforme (GBM) is the most common and most malignant primary brain tumor occurring during adulthood. The incidence of GBM is nearly 5 cases per 100,000 population per year. The standard of care for newly diagnosed GBM includes surgical resection when possible, followed by radiotherapy and concomitant and adjuvant chemotherapy with temozolomide. Imaging modalities used in nuclear medicine, namely positron emission tomography (PET) and single-photon emission computed tomography (SPECT) have been employed towards the evaluation of brain tumors. Herewith, we discuss the value of the above imaging techniques in the assessment of GBM aggressiveness, in the distinction of treatment induced necrosis from glioma recurrence, in the estimation of overall prognosis and in the evaluation of treatment response in patients with GBM.