Despite numerous diagnostic possibilities the early diagnosis of pancreatic cancer is still an exemption. Only 10-15% of patients are diagnosed at a stage where the tumor is resectable. Thus, most patients are treated with a palliative intention at first diagnosis. Palliative treatment comprises different therapeutic modalities involving radiochemotherapy and conventional chemotherapy. Chemotherapy, in particular, has been challenged by several new concepts involving combination regimens and the addition of targeted therapies to conventional therapeutic regimens. This review offers a critical presentation of current concepts in the palliative treatment of pancreatic cancer, discussing the problems of each and pointing to the development of new therapeutic strategies.