Response is the logical outcome measure of a treatment in a clinical or research setting. Objective response assessment involves the use of a test to segregate patients who are likely to experience improved survival from those who are not. Early and accurate response assessment is critical for determining therapy effectiveness in clinical settings, for effective trial designs comparing two or more therapies, and for modulating treatment on the basis of response (ie, response-adapted therapy). 2-[fluorine 18]fluoro-2-deoxy-d-glucose (FDG) PET/CT can provide both functional and structural information about a disease process. It has been used at several stages of patient management, including imaging-based tumor response assessment, for various malignancies. FDG PET/CT can be used to differentiate patients with lymphoma who have a residual mass but no residual disease after treatment (ie, complete responders) from those who have a residual mass and residual disease after treatment. Similarly, in solid malignancies, the functional changes in glucose uptake and metabolism precede the structural changes (commonly seen as tumor shrinkage) and necrosis. Response assessment criteria have been developed on the basis of findings on FDG PET/CT images and are continuously being revised to ensure standardization and improve their predictive performance. Published under a CC BY 4.0 license. Quiz questions for this article are available through the Online Learning Center.