By using experimental combined adjuvant and neoadjuvant therapies in pancreatic ductal adenocarcinoma patients, progress has been made in survival, clinical benefit response, and even downstaging of tumors to allow surgical resection. The use of combined modality approaches in pancreatic ductal adenocarcinoma is associated with increased gastrointestinal toxicity, which may manifest as bowel wall abnormalities and peripancreatic inflammatory changes on multiphasic multidetector computed tomography and affect assessment of the pancreatic tumor. During preoperative neoadjuvant therapy, occult metastatic disease may be given the opportunity to manifest, thus preventing the morbidity of attempted resection or laparotomy. Although advances in the neoadjuvant and adjuvant treatment of patients with pancreatic carcinoma have thus far yielded only a modest impact on prognosis, in the future greater numbers of patients will undergo these treatments in searching for cure. As therapy with targeted agents evolves, the team of gastroenterologists, oncologists, surgeons, and radiologists caring for these complex patients should become familiar with the varied tumor response and host reactions to newer therapies that may be depicted on multiphase multidetector computed tomography.