Response to perioperative chemotherapy or chemoradiation can hardly be predicted on the basis of molecular marker analyses. In contrast, by means of metabolic and molecular imaging using positron emission tomography, response can be assessed as early as 14 days after the start chemotherapy for many tumors. There is no doubt that the prognosis of patients with surgically resected tumors is much better in the case of a response to chemotherapy or chemoradiation. Important consequences can be deduced from this regarding the indications for perioperative therapies, the radicality of surgery or the surgical indications per se. In the following, we delineate the current knowledge on response prediction and early response evaluation in selected tumor entities and draw possible conclusions for clinical practice and future clinical studies.