OBJECTIVES:  The standard of care for first-line (1L) therapy in GBM, a high-grade brain tumor with poor prognosis, is maximal safe resection followed by radiation therapy (RT) concurrent with temozolomide and maintenance temozolomide. However, beyond 1L, there is no standard of care that improves overall survival and there are limited treatment options, especially for elderly/frail patients. This analysis characterized real-world treatment patterns for US elderly GBM patients. METHODS:  Newly diagnosed patients ≥66 years of age with histologically confirmed GBM between 2007 and 2011 were identified from the SEER-Medicare linked database. Patients were followed from diagnosis to death, Medicare disenrollment, HMO enrollment, or 12/31/2013 to characterize their treatment patterns with respect to receipt of systemic treatments—in 1L, second-line (2L) and third or subsequent lines (3L+). The proportion of patients receiving RT was reported. RESULTS:  Among 3,012 eligible GBM patients (median age: 74 years; male: 53%; Charlson comorbidity index [CCI] ≥2: 13%; and median follow-up: 5 months), 1,459 (48.5%) received systemic therapy ± RT, 841 (27.9%) received RT alone, and 712 (23.6%) did not receive any intervention. Among patients who received 1L (n=1,459), 1,169 (80.1%) received temozolomide. Of 1L patients, 483 (33.1%) and 126 (8.6%) received 2L and 3L+, respectively. The most prevalent 2L and 3L systemic therapies were bevacizumab/chemotherapy (44.7% of 2L; 58.7% of 3L) followed by bevacizumab monotherapy (32.9% of 2L; 19.1% of 3L). Median (IQR) durations of 1L, 2L, and 3L therapies were 72 (43–196), 98 (43–207), and 84 (41–162) days, respectively. CONCLUSIONS:  Only about half of elderly GBM patients received systemic therapy at 1L (mostly temozolomide), and about a third of those were given a subsequent line of systemic (mostly bevacizumab-based) therapy. This analysis documents an unmet medical need for elderly GBM patients despite a host of clinical trial activity, especially in later lines.