OBJECTIVES: Approved treatment options for patients with recurrent GBM yield limited survival and QoL benefits. A systematic review was conducted to summarize OS, QoL, and NF among patients with recurrent GBM. METHODS: Eligible English-language publications (01/2005–10/2014) were identified using EMBASE, MEDLINE, and the Cochrane Library. RESULTS: Fifty publications were identified. Among bevacizumab-naïve patients treated with monotherapies, median OS ranged from 6.4–9.3 months with initial bevacizumab treatment, 6.6–9.4 months with other targeted therapies (enzastaurin, cediranib, and sunitinib), 7.1–11.7 months with chemotherapies (lomustine, verubulin, and temozolomide), and 10.9–11.4 months with the anti-hepatocyte growth factor monoclonal antibody rilotumumab. Among those treated with combination therapies, median OS ranged from 8.7–16.0 months with bevacizumab + chemotherapy, 5.6 months with bevacizumab + sorafenib, and 9.4 months with cediranib + lomustine. Among patients with prior bevacizumab treatment, median OS was 3.4 months with verubulin, 4.4 months with sunitinib, and 3.4–3.6 months with rilotumumab. Among studies not specifically reporting outcomes for bevacizumab-naïve or -experienced patients, median OS ranged from 4.4 months with temsirolimus to 24.5 months with fotemustine. Factors that paralleled longer OS included male sex, younger age, fewer prior therapies, faster brain tissue diffusion on imaging, longer time to recurrence, smaller tumor volume, better performance status, and methylated O-methylguanine-DNA methyltransferase promoter regions. Eight studies assessed the humanistic burden on patients. Baseline QoL and NF among these patients were worse compared with both the general population and patients with other cancers. No studies reported treatment-related improvements in QoL or NF. CONCLUSIONS: Currently available therapies for recurrent GBM are associated with limited OS duration and a lack of improvements in QoL or NF. Among bevacizumab-naïve patients, initiation of bevacizumab or other mono- or combination therapies resulted in median OS less than 1.4 years, indicating a consistent unmet need in this population.