The currently accepted standard of care for primary glioblastoma (GBM) consists of maximal surgical resection followed by fractionated external beam radiotherapy (EBRT) with concomitant temozolomide chemotherapy. The role of stereotactic radiosurgery (SRS) in the treatment of GBM is not well defined, but SRS has typically been applied as a salvage therapy for GBM recurrence. This paper reviews our single institution experience using gamma knife radiosurgery (GKRS) for the treatment of GBM. Thirty-six patients treated with GKRS for pathologically proven GBM at LSU Health in Shreveport from February 2000 to December 2013 were identified and analyzed. Patient characteristics, treatment variables, and survival were correlated. Seven patients received GKRS in the immediate postoperative period for an average tumor volume of 10.9 cm3, and 29 patients were treated for a recurrent average tumor volume of 11.4 cm3 with a prescribed dose ranging from 10 to 20 Gy at the 50 % isodose line. The median overall survival was significantly higher in recurrence group compared to up-front group [7.9 months (0.77–32.1 months) vs. 3.5 months (range 0.23–11.7 months) respectively, (p = 0.018)]. The predictive factors for improved survival in the patients with GBM were as follows: Karnofsky performance scale (KPS) > 70 (p = 0.026), age ≤ 50 years (p = 0.006), absence of neurodeficits (p = 0.01), and initial postoperative treatment with EBRT (p = 0.042). Adjuvant therapy with GKRS following GBM recurrence demonstrates statistical superiority over immediate postoperative boost therapy.