In about 30-40% of all patients with pancreatic cancer a locally advanced lesion without distant metastases is found at primary diagnosis and the tumor is mostly nonresectable due to the close vicinity to blood vessels. Neoadjuvant treatment strategies, such as neoadjuvant radiochemotherapy offer the possibility to achieve substantial tumor reduction so that secondary resectability can be achieved. Therefore, treatment decisions should be made in an interdisciplinary context. In the future, innovative study protocols as well as novel radiation modalities, such as carbon ions can open new horizons in the treatment of this patient population. Additionally, molecular markers may help to stratify patients for different treatment schedules.