The gold standard for determining the efficacy of biomedical therapies is the detection of a significant difference between the therapeutic effects of an active pharmacological agent or procedure and a matched inert placebo in a randomized controlled trial. Detecting this difference has become a challenge for medicine, especially for outcomes that are based on patient self-rated scales. Yet factors that contribute to placebo responses have received scant attention. In this issue of Science Translational Medicine, Bingel et al. report on an example of how noninvasive whole-brain imaging contributes to our understanding of brain-based placebo effects. Here we highlight ways in which neuroimaging is catalyzing a revolution in society's perspective of placebo effects by providing a compelling visualization of how brain activities that reflect a person's thoughts, feelings, and past experiences can enhance or antagonize his or her response to a medical treatment.