2-deoxy-2- Ffluoro-D-glucose ( FFDG) is a promising tool to support the evaluation of response to either target therapies or immunotherapy with immune checkpoint inhibitors both in clinical trials and, in selected patients, at the single patient's level. The present review aims to discuss available evidence related to the use of FFDG PET (Positron Emission Tomography) to evaluate the response to target therapies and immune checkpoint inhibitors. Criteria proposed for the standardization of the definition of the PET-based response and complementary value with respect to morphological imaging are commented on. The use of PET-based assessment of the response through metabolic pathways other than glucose metabolism is also relevant in the framework of personalized cancer treatment. A brief discussion of the preliminary evidence for the use of non-FDG PET tracers in the evaluation of the response to new therapies is also provided.