Due to the worse prognosis of patients with adenocarcinoma of the pancreas, new combined treatment modalities as adjuvant and neoadjuvant radio-chemotherapy, particularly with more modern chemotherapeutic agents, for patients with resectable and unresectable tumors are under investigation. For some reasons, the neoadjuvant setting seems to be better. However, these results are not proven by prospective randomized clinical trials. Therefore, these trials are necessary to define the treatment of choice in these patients. IORT is a helpful tool to improve local control. However, these aggressive multimodality approaches are only indicated in a minority of patients. In patients with unresectable tumors and good condition, combined radio-chemotherapy remains the treatment of choice.