Surgical resection is the only known treatment associated with long-term survival in pancreatic adenocarcinoma. While adjuvant therapy has shown a clear survival benefit, neoadjuvant chemotherapy has gained interest due to its ability to prioritize the treatment of micrometastatic disease prior to resection and improve chemotherapy tolerance prior to a major operation. Investigations have focused on evaluating the survival benefit of neoadjuvant therapy using single and combination chemotherapy as well as radiation therapy. Landmark trials in localized pancreatic cancer have paved the way for the standard use of neoadjuvant therapy for pancreatic adenocarcinoma.