The current method for assessing the response to therapy of glial tumors was described by Macdonald et al. in 1990. Under this paradigm, response categorization is determined on the basis of changes in the cross-sectional area of a tumor on neuroimaging, coupled with clinical assessment of neurological status and corticosteroid utilization. These categories of response have certain limitations; for example, cross-sectional assessment is not as accurate as volumetric assessment, which is now feasible. Disentangling antitumor effects of therapies from their effects on blood-brain barrier permeability can be challenging. The use of insufficient response criteria might be overestimating the true benefits of drugs in early-stage studies, and, therefore, such therapies could mistakenly move forward into later phases, only to result in disappointment when overall survival is measured. We propose that studies report both radiographic and clinical response rates, use volumetric rather than cross-sectional area to measure lesion size, and incorporate findings from mechanistic imaging and blood biomarker studies more frequently, and also suggest that investigators recognize the limitations of imaging biomarkers as surrogate end points.