FDG PET/CT (fluorodeoxyglucose (FDG)-positron emission tomography (PET) computed tomography (CT)) imaging reflects functional-metabolic changes occurring within the malignant process in response to therapy. Since these changes usually precede anatomic alterations, this imaging technique is highly valuable in assessing response during and after therapy and is superior to CT. FDG PET/CT following initiation of cancer therapy has a prognostic value, predicting progression free survival and overall survival. In some malignancies FDG PET/CT can guide personalized medicine by tailoring therapy in accordance with the metabolic cancer response in the individual patient. In lymphoma patients, including Hodgkin’s disease (HD) and diffuse large B-cell lymphoma (DLBCL), FDG PET/CT is useful for monitoring response and guiding therapy, both after and early during therapy. Various quantitative and visual criteria systems are used for assessing cancer response to therapy by FDG PET/CT. Acquaintance with these interpretation methods and their adjustment to new anti-cancerous mechanisms such as in immunotherapy, is important for accurate imaging and meaningful interpretation. Large prospective meticulously performed studies, using standardized methodology, are required to further establish and expand the use of FDG PET/CT for the assessment of response to therapy in various malignancies.