Neoadjuvant chemotherapy has become common practice in the management of patients with non-metastatic pancreatic adenocarcinoma. This strategy helps better select patients who would benefit from surgical resection and also increase the number of patients amenable to surgical resection whose tumor seemed too locally advanced on initial imaging. However, several studies have shown that the radiological evaluation of the response after neoadjuvant therapy is difficult for pancreatic carcinoma. This article reviews the scientific basis of neoadjuvant therapy for non-metastatic pancreatic cancer and provides an update on tumor response evaluation with imaging after neoadjuvant treatment.