Pancreatic ductal adenocarcinoma is one of the most aggressive human malignancies, with an overall 5-year survival rate of less than 4%. On the molecular level, an increasing number of genetic and epigenetic alterations have been discovered, with a particular focus on growth factors and related pathways. Small-molecule tyrosine kinase inhibitors, antibodies, and other approaches have been developed in recent years to target these signal transduction pathways, and first clinical trials show encouraging results. In addition, molecular alterations have been identified that enable the cancer cells to invade the perineurium and the retroperitoneal space, thus explaining at least in part the high rate of local recurrence and the severe pain syndrome. Technically, pancreatic surgery has advanced, with acceptable morbidity and mortality rates in high-volume centers. Randomized controlled trials are increasingly carried out to define the best palliative and adjuvant therapy for this disease. Translational research combined with clinical trials will hopefully lead to improved survival and better quality of life for pancreatic cancer patients in the future.