The incidence of brain metastasis has increased over the past decade. Standard treatment options for brain metastases include whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS) and surgery for patients with operable lesions and either mass effect or need for histologic confirmation of the diagnosis. Patients are living longer due to improvements in systemic therapeutic approaches, included targeted therapies such as inhibition of vascular endothelial growth factor (VEGF) using the monoclonal antibody bevacizumab (Bev). A recent phase I trial (REBECA) investigated adding Bev to whole-brain radiation for patients with brain metastasis from solid tumors. In this Perspectives article, we discuss the results of the REBECA trial in context of advancements in radiation and medical oncology in the era of targeted therapies, and discuss pertinent questions of interest in this field.