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Patients with pancreatic cancer have a poor prognosis although systemic treatment has slightly improved the outcome for those with advanced pancreatic cancer. The approach to a patient with pancreatic cancer remains a great challenge. Patients often present with advanced disease and many are already in poor general condition at the time of diagnosis. Today, surgery remains the only curative therapeutic option. A small number of pancreatic adenocarcinomas, however, are resectable and relapses after surgery are very frequent. The reference treatment in patients with metastatic pancreatic cancer is gemcitabine. The median survival of patients with advanced pancreatic cancer who are treated with gemcitabine is ∼6 months and only ∼20% of patients will be alive at 1 year. Combinations of gemcitabine with new cytotoxic agents and with novel targeted agents hold the promise for improving the outcome. Randomized phase III studies are, however, still ongoing. Since most patients will relapse after complete surgical resection of pancreatic cancer, a search for a better adjuvant or neoadjuvant treatment is important. Although several randomized studies have suggested an improved outcome for a postoperative chemoradiotherapy or chemotherapy, the role of an adjuvant treatment remains today controversial. Randomized phase III studies are ongoing. A neoadjuvant strategy might therefore also play a role, but phase III studies are lacking. The systematic evaluation of new drugs in well designed clinical trials and the search for new molecular targets for treatment are crucial in our aim to improve the outcome for patients with pancreatic cancer.