Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal and aggressive malignancies and is the fourth leading cause of cancer-related death in the industrialized countries. The emergence of combination chemotherapy in the setting of metastatic pancreatic adenocarcinoma has led to its evaluation. The combinations of gemcitabine and nab-paclitaxel, and FOLFIRINOX have been compared to gemcitabine alone in two large phase III trials, respectively. Some new drugs are under evaluation in pancreatic cancer but at the moment there is no positive evidence for translating this to the adjuvant setting. Translational data from the recent phase III trials will likely contribute to progress with the adjuvant approach. Molecular subtyping of PDAC could drive choice of therapy and implementation of neoadjuvant strategies and is likely to contribute in the near future to continuously improving the curative approach to pancreatic cancer.