Exocrine pancreatic cancer has a very poor prognosis. R0 resection of the tumor is to date the only potentially curative approach, but less than 20% of patients are eligible for a curative surgery at diagnosis. Until recently, gemcitabine was the standard treatment for advanced and metastatic pancreatic cancer patients, since it was shown more than a decade ago to induce clinical benefit and to improve survival when compared to weekly bolus 5-fluorouracil. In order to improve patients’ outcome many trials have, during the last 10 years, explored the pharmacokinetic modulation of gemcitabine and combination therapies with gemcitabine and other anti-cancer agents with consistent negative results. It is finally a trial assessing the efficacy of a combination chemotherapy without gemcitabine: the FOLFIRINOX regimen, reported this year, that has shown for the first time a significant improvement in progression free and overall survivals. In parallel, many trials testing new targeted agents in these patients are currently ongoing. After 10years without significant progress in the treatment of pancreatic cancer patients, the hope that a significant improvement in the outcome of these patients can be achieved has been raised.