Median as well as overall survival of pancreatic cancer patients in the advanced stage is extremely low despite advances in cancer therapy regarding tumor cell biology, therapy resistance, and diagnosis. In matters of chemoradiation therapy (CRT) in locally advanced pancreatic cancer, favorable positive effect has been reached with different radiotherapy proceedings such as intraoperative radiation therapy with or without external chemo-/radiation therapy or with CRT alone with regard to local tumor pain, local tumor remission, or local control of disease and overall survival. Primary (chemo-) radiation therapy only rarely leads to local remission. Intraoperative radiation therapy (IORT) merely reaches pain palliation in most cases. By administering up-to-date primary CRT, especially with gemcitabine-associated CRT, local remission in up to 50% of patients can be observed. By applying neoadjuvant CRT, better resectability and the reduction of postoperative positive lymph node metastasis has been seen in patients with resectable or possibly resectable pancreatic cancer. With primary CRT, resectability can also be achieved in patients with primary unresectable pancreatic cancer. It has been shown at the evaluation of patients' progression samples--either treated with neoadjuvant or primarily with radiotherapy (with conventional radiation technique)--that the rate of local recurrence or local progression can be reduced in comparison with historical cohorts. By contrast, the rate on distant metastases was not affected. Whereas concurrent CRT leads to favorable local tumor control, this procedure has a minor effect as to the survival in most of the studies. Because metastases occur mostly out of the irradiation field and because of partly advanced local tumor progression, the concept of combined CRT with continuing chemotherapy was developed. Median survival of pancreatic patients in the advanced stage is approx. 3-5 months, with a 12-month survival probability of 10% despite advances in cancer therapy. On the other hand, the 5-year survival probability is 0.4%-3.0%. The causes of such a dismal prognosis can be understood first of all in the commonly late diagnosis, second in the aggressive tumor cell biology with continuing therapy resistance, and finally because an acceptable resection rate can be achieved only in specialized centers. Only 10%-15% of patients can be resected after the diagnosis of pancreatic cancer. Resection is considered a potential curative therapy. However, median survival of these patients amounts to only 13-18 months, with a 5-year survival of 10%-20%. The survival rate did not improve with a radical resection and extended lymphadenectomy. Furthermore, 15%-30% of primary nonmetastatic pancreatic cancer is unresectable due to extended vessel infiltration at time of diagnosis. The prognosis for these patients is very dismal due to lack of specific therapy; moreover, median overall survival is a maximum of 6-8 months.