Rapid acquired resistance to antiangiogenic therapies such as bevacizumab limits clinical utility of this approach in highly vascular tumors including glioblastoma multiforme. β1 integrins represent a critical pathway for the promotion of malignant progression and acquired therapy resistance in cancer cells through adhesive interactions with the surrounding tumor microenvironment. Using a multimodal approach, it was found that the β1 integrin subunit was functionally upregulated in patient glioblastoma specimens with acquired resistance to bevacizumab. Knockdown or inhibition of the β1 integrin subunit with neutralizing monoclonal antibodies promoted reversion of malignant phenotype and attenuated in vivo growth of bevacizumab-resistant glioblastoma xenografts. For details, see article by Carbonell and colleagues on page 3145.