The standard treatment of resectable pancreatic cancer is surgery followed by adjuvant chemotherapy. Due to the complication rate of pancreatic surgery and the high rate of primary irresectability, neoadjuvant concepts are increasingly used for pancreatic cancer. Neoadjuvant therapy is better tolerated than adjuvant and might decrease the surgical complication rate from pancreatic surgery. In contrast to neoadjuvant chemoradiation, the nutritional status improves during neoadjuvant chemotherapy. Also, the survival of patients who develop postoperative complications after neoadjuvant therapy is comparable to those without complications whereas the survival of patients who underwent upfront surgery and then develop surgical complications is impaired. Moreover, large data base analyses suggest a down-sizing effect and improvement of overall survival by neoadjuvant therapy. Neoadjuvant chemotherapy appears to be equally efficient in converting irresectable in resectable disease and more efficient with regard to systemic tumor progression and overall survival compared to neoadjuvant chemoradiation therapy. Despite these convincing findings from mostly small phase II trials, neoadjuvant therapy has not yet proven superiority over upfront surgery in randomized trials.