The prognosis of pancreatic carcinoma is dismal. Its main reason can be attributed to the difficult early diagnosis. In fact, at diagnosis most patients show advanced disease. In recent years, studies on the biomolecular characteristics of this disease have been conducted. The obtained results have favored the understanding of the basic mechanisms of the biologic aggressiveness and the resistance to chemoradiation of pancreatic carcinoma. They include the frequent oncogene activation as well as the similarly frequent suppressor gene inhibition. Based on this new knowledge, novel therapeutic strategies have been identified and treatments of targeting the ras oncoprotein or mutated p53, metalloproteinase inhibitors and tyrosine kinase receptor inhibitors (trastuzumab and cetuximab) together with antiangiogenic therapies are under experimentation.