Pancreatic cancer remains the fourth leading cause of cancer-related deaths in the United States. Risk factors include family history, smoking, chronic pancreatitis, obesity, diabetes mellitus, heavy alcohol use, and possible dietary factors. Because more than two-thirds of adenocarcinomas occur in the head of the pancreas, abdominal pain, jaundice, pruritus, dark urine, and acholic stools may be presenting symptoms. In symptomatic patients, the serum tumor marker cancer antigen 19-9 can be used to confirm the diagnosis and to predict prognosis and recurrence after resection. Pancreas protocol computed tomography is considered standard for the diagnosis and staging of pancreatic cancer. Although surgical resection is the only potentially curative treatment for pancreatic ductal adenocarcinomas, less than 20% of surgical candidates survive five years. The decision on resectability requires multidisciplinary consultation. Pancreatic resections should be performed at institutions that complete at least 15 of the surgeries annually. Postoperatively, use of gemcitabine or fluorouracil/leucovorin as adjuvant chemotherapy improves overall survival by several months. However, more than 80% of patients present with disease that is not surgically resectable. For patients with locally advanced or metastatic disease, chemoradiotherapy with gemcitabine or irinotecan provides clinical benefit and modest survival improvement. Palliation should address pain control, biliary and gastric outlet obstruction, malnutrition, thromboembolic disease, and depression.