Despite great efforts in the field of preclinical and clinical research, pancreatic cancer is still one of the most devastating cancer diagnoses and nearly always results in death. With neoadjuvant chemoradiotherapy higher R0 resection rates can be achieved in pancreatic cancer and may even lead to a secondary resection in primarily inoperable tumors. Patients who experience a disease progression due to aggressive tumor biology can be spared the unnecessary morbidity of resection by neoadjuvant therapy. Even in the adjuvant situation the rates of local relapse can be significantly reduced by combined chemoradiotherapy. Through progress in radiation techniques the toxicity of combined chemoradiotherapy could be lowered. If symptoms of the metastasized disease are caused by localized solitary or more widespread tumor manifestation, chemoradiotherapy should be considered for a rapid symptom relief. The adjunct of various biologicals to chemoradiotherapy is a promising new way to improve the prognosis of pancreatic cancer. Results from initial trials to clarify this concept are expected soon. Despite all progress in radiation techniques and in systemic therapy of pancreatic cancer, psychooncological care and good nutrition is of especially high importance in the care of this group of patients.