Pancreatic cancer remains the fourth leading cause of cancer-related deaths in adults in this country. Its etiology is unknown, and there is currently no effective method of early diagnosis. Although this article will focus on the proper management of patients with potentially resectable disease, such patients represent the minority of those diagnosed with pancreatic cancer. Therefore, at most medical centers, clinical and basic science research is proceeding in parallel: while attempting to optimize the length and quality of life of patients with localized pancreatic tumors, research is also focusing on developing improved strategies for early diagnosis and effective systemic therapy. For patients with localized pancreatic cancer, data from our institution support the use of detailed preoperative imaging studies to allow accurate assessment of tumor resectability. Patients found to have locally advanced or metastatic disease do not undergo laparotomy; biliary decompression, when necessary, is performed utilizing endoscopic or laparoscopic techniques. Pancreaticoduodenectomy is performed on carefully selected patients as part of a protocol-based clinical research program emphasizing the importance of multimodality management for patients with potentially resectable adenocarcinoma of the pancreatic head.