Pancreatic cancer is the fourth leading cause of cancer deaths in the United States. Surgical resection offers the only hope of cure, though the addition of chemoradiation in the adjuvant setting has been shown to improve survival over surgery alone. Many patients are unable to receive adjuvant therapy due to prolonged postoperative recovery. For this reason, administration of chemoradiation preoperatively (neoadjuvant) has been proposed as an alternative to postoperative treatment. In patients with resectable disease, neoadjuvant therapy results in similar survivals compared to postoperative therapy, with a greater proportion of patients able to complete treatment. For selected patients with borderline or unresectable disease, neoadjuvant therapy offers the potential for tumor downstaging and increasing the likelihood of a margin-negative resection. This article reviews the use of neoadjuvant therapy in the treatment of pancreatic cancer.