In the last decades, many attempts were made to optimize the biological effect of RT in the treatment of pancreatic carcinoma. The use of combined radiotherapy and chemotherapy was certainly successful, with the most promising results achieved with the combination of several drugs with RT or with innovative modalities of administration of concomitant chemotherapy. A dose effect in resected tumors seems suggested by some studies; while the use of high doses in inoperable tumors did not result in significant advantages in terms of response and outcome, a significant correlation between dose and toxicity was observed. Altered fractionations were not studied systematically, though an accelerated-hypofractionated (30 Gy in 10 fractions) treatment is indicated as feasible in combination with concomitant chemotherapy with results similar to those achieved with conventional fractionations and a markedly shorter duration. Based on the small improvements recorded in the treatment of these tumors, the evaluation of newer treatment modalities seems justified.