Despite recent advances in multi-modality and targeted antineoplastic therapy, efforts to improve clinical outcomes for patients with pancreatic adenocarcinoma remain challenging. The potential for cure is applicable only to patients whose tumors are initially resectable or those with borderline, potentially resectable locally advanced tumors. However, these patients constitute < 10% of all newly diagnosed patients with pancreatic cancer . For most patients with pancreatic cancer, the goal of therapy is palliation, and the prognosis is very poor. Patients with locally advanced pancreatic cancer have a median life expectancy of 6–10 months, and patients with metastatic disease have an even shorter median survival of approximately 3–6 months . Current standard and experimental therapeutic options for patients with locally advanced and metastatic pancreatic cancer are evolving and are discussed below. A multi-disciplinary approach is required for the proper assessment and treatment of patients with locally advanced pancreatic cancer. Optimal imaging of the pancreas and its surrounding tissues may delineate tumors that truly are unresectable and those with “borderline” resectability. Whereas the median survival of patients with unresected locally advanced pancreatic cancer is 6–10 months , survival times of 21 months can potentially be achieved in patients who have had resection of their tumor after preoperative therapy . This survival time is comparable to the median survival time achieved with upfront pancreatic cancer resection followed by adjuvant therapy.