Perioperative chemotherapy in stage II and stage III gastric cancer is now accepted as a standard of care in the Western world. Two randomized phase III studies have shown improved survival for patients with induction chemotherapy followed by surgery compared with surgery alone. It is generally accepted that patients who respond to induction therapy have a significantly improved survival compared with that in nonresponding patients. Unfortunately no prospectively tested markers predicting response and/or prognosis are available for clinical practice. In adenocarcinomas of the esophagogastric junction (AEG), fluorodeoxyglucose-positron emission tomography (FDG-PET) prospectively was established as a surrogate predicting response and prognosis. The MUNICON (Metabolic response evalUatioN for Individualisation of neoadjuvant Chemotherapy in oesOphageal and oesophagogastric adeNocarcinoma) I study confirmed prospectively the usefulness of early metabolic response evaluation and showed the feasibility of a PET-guided treatment algorithm. These findings are an important step forward in the tailoring of multimodal treatment in accordance with tumor biology. In gastric cancer, we have analyzed FDG-PET in a prospective study. In gastric cancer the issue is more complicated, because about 30% of gastric cancers cannot be visualized with sufficient contrast for quantification. Insufficient FDG uptake is mostly associated with diffuse-type gastric cancer with signet ring cells and mucinous content. In FDG-avid patients, FDG-PET can be used for response evaluation, comparable to that in AEG. The prognosis of FDG-nonavid patients is similar to that in metabolic nonresponders. The addition of new tracers such as fluorothymidine may increase the sensitivity of PET in the future. Treatment concepts such as immediate resection after only 2 weeks of induction therapy with or without adjuvant treatment could be considered in metabolic nonresponders, or modified chemotherapy regimens, possibly including biologically targeted drugs, could be considered in those with FDG-nonavid tumors.