Pancreatic cancer is the fourth leading cause of cancer-related death in the USA. The disease has a high mortality rate and the 5-year survival rate is estimated to be 4%. Currently, surgical resection is only possible in 20% of patients; even then, the overall 5-year survival rate is only 25%. As such, surgical therapy alone is not sufficient for pancreatic carcinoma, and prospective investigation of additional modalities is crucial. Numerous negative trials have shown that chemotherapy alone is the standard of care after resection of pancreatic carcinoma. However, results remain poor and progress with new drugs is needed in this setting. For locally advanced disease, the situation is more complicated; the ideal chemoradiation schedule has not been clearly defined, and improvements could come in the near future from the use of new radiotherapy tools and targeted therapies. For advanced disease, chemotherapy alone has given very disappointing results. A multidisciplinary approach combining biological assessment of targets with clinical trials to evaluate new targeted drugs should be considered.