Pancreatic cancer is one of the most aggressive and devastating human malignancies with a mortality rate over 90%.Pancreatic cancer ranks as the fifth leading cause of cancer-related deaths in Western countries.The majority of patients with pancreatic cancer presents with metastatic disease (~55%) or locally advanced disease (~35%) at the time of diagnosis.Surgery offers the only possibility of cure, but this is possible in only a small number of patients (10-20%).It is also estimated that 70% of patients eligible for surgery are not evaluated for resection.Lack of effective adjuvant therapy has also contributed to the nihilistic attitude to pancreatic cancer.The role of radiation therapy whether in neoadjuvant setting or postoperatively is still controversial and debatable.Advances, controversies and multimodality therapy will be discussed; new diagnostic and therapeutic strategies will be explored and current knowledge and perspectives of molecular targeted therapy will be evaluated.Innovative approaches with gene therapy clinical trial will also be presented.