In spite of the high mortality in pancreatic cancer, significant progress is being made. This review discusses multimodality therapy for patients with pancreatic cancer. According to several phase II trials and Gastrointestinal Tumor Study Group results, improvements in locoregional control and survival may be achieved when chemotherapy is added to radiation for locally advanced pancreatic cancer. Radiosensitizing chemotherapy agents such as 5-fluorouracil, gemcitabine, paclitaxel, and cisplatin have shown promise. Selected patients with locally advanced disease have been downstaged with chemoradiation, facilitating surgical resection. For patients with resectable disease, the completion of Radiation Therapy Oncology Group study 97-04 represents a major achievement and brings gemcitabine into the forefront of adjuvant therapy. Neoadjuvant chemoradiation may eliminate the delay of initiating adjuvant treatment and spare unnecessary surgery for patients with rapid systemic progression. Molecular agents are being combined with chemoradiation in an attempt to delay or prevent systemic progression. © 2003 Elsevier Inc. All rights reserved.