Pancreatic ductal adenocarcinoma (PDA) remains among the most challenging malignancies to treat. At diagnosis, the tumor often already extends beyond the confines of the pancreas, spreading to an extent such that primary surgery with curative intent is very rarely feasible. Considerable momentum is now being given to a treatment strategy involving neoadjuvant chemotherapy or chemotherapy and radiation therapy in patients with nonmetastatic PDA. The main advantage of this strategy is better selection of patients likely to benefit from curative-intent surgery through the achievement of negative resection margins. Patients with rapidly progressive disease are identified and are spared ineffective surgery with its attendant morbidity. Neoadjuvant therapy can downstage tumors classified as locally advanced at initial imaging studies to resectable tumors. However, the imaging study evaluation of the response to neoadjuvant therapy is extremely complex. Thus, the diagnostic performance of imaging studies is not sufficient to ensure the accurate selection of patients in whom negative-margin resection is likely to be achieved. More specifically, standard criteria for predicting vascular invasion, based on the amount of tumor-vessel contact, are not valid after neoadjuvant therapy. ©RSNA, 2018.