INTRODUCTION: Glioblastoma multiforme (GBM) is the most common high grade primary brain tumor in adults. Despite significant advances in treatment, the prognosis remains poor. Bevacizumab (BVZ) and irinotecan (CPT-11) are currently being investigated in the treatment of GBM patients. Although treatment with BVZ and irinotecan provides impressive response rates (RR), it is still uncertain if this treatment translates into improved clinical benefit in GBM patients. AREAS COVERED: This review discusses the clinical efficacy, safety and difficulties regarding response evaluation when treating with BVZ and CPT-11 in recurrent GBM. Particular attention is placed on the literature and a discussion on whether treatment with BVZ and CPT-11 improves clinical outcome. Antiangiogenic treatment has led to difficulties when evaluating objective response by the conventional MacDonald criteria. In the present paper the authors discuss selected key aspects of this treatment modality. A literature search was performed using PubMed in February 2011. EXPERT OPINION: BVZ + irinotecan leads to high RR and to an increased 6-month progression-free survival. However, no improvement in median overall survival has been observed compared with conventional chemotherapy. Nevertheless, the GBM patients who respond to treatment with BVZ and irinotecan have survived significantly longer than non-responders, indicating that it could be beneficial for a selection of patients to receive this treatment.