The purpose of this review is to assess the palliative effect of re-irradiation in adult patients with recurrent supratentorial glioblastoma (GBM) previously treated with adjuvant or primary radiation therapy, with or without chemotherapy. From a comprehensive literature search, studies were identified reporting on survival, progression, and quality of life endpoints including, but not limited to, EORTC QLQ-C30 questionnaire, clinical symptoms, and ability to reduce dexamethasone. Data from more than 300 GBM patients (grade 3 anaplastic gliomas were excluded) demonstrate that re-irradiation yields 6-month PFS of 28% to 39% and 1-year overall survival of 18% to 48%, without additional chemotherapy (median value 26%). Patients with Karnofsky performance status <70 appeared to be at higher risk of early progression and apparently had lesser benefit from re-irradiation. Clinical improvement was observed in 24% to 45% of the patients. Most studies suggest that stabilization of the performance status is a realistic aim. In the studies reporting on corticosteroid usage during and after re-irradiation, 20% to 60% of the patients achieved a reduction in steroid dependency. Serious late toxicity was uncommon, especially after conventional treatment and fractionated stereotactic radiotherapy (FSRT). In light of recent technological advances such as FSRT and intensity modulated radiotherapy, which permit maximal sparing of normal brain, re-treatment seems attractive, and deserves scientific validation. Even fraction sizes of 3 to 5 Gy seem to be well tolerated in limited-volume recurrences as long as the total dose is limited to 30 to 35 Gy. Salvage chemotherapy or targeted agents should be prospectively tested against re-irradiation alone.