Accurate and early evaluation of tumor response to chemotherapy is a growing clinical need for optimal management of oncology patients. This is even more warranted by the lack of appropriate response evaluation criteria to new molecularly targeted anticancer therapies. In the two last decades, new developments in the field of nuclear oncology have allowed the introduction of various radiopharmaceuticals to be used on dedicated imaging devices. In the present chapter, we report the added value that positron emission tomography (PET) with 18F-fluorodeoxyglucose (18FDG) may offer to assess tumor response to treatment. PET is a high-end imaging technology using 18FDG as metabolic tracer that mimics the biochemical behavior of the natural glucose molecule. Because most tumor types exhibit increased glucose metabolism, the imaging of 18FDG uptake within cancer tissues prior to any treatment enables the metabolic technique to follow tumor responsiveness sequentially after one or several courses of chemotherapy. Moreover, metabolic tumor response evaluated by 18FDG PET often precedes morphological tumor changes measured by computed tomography or magnetic resonance imaging. So far, the suboptimal proper ties of 18FDG tracer and the lack of standardized methodology in PET imaging remain objective limitations for qualitative and quantitative assessment of chemosensitivity using the metabolic method.