Because most patients with pancreatic and biliary cancer have advanced disease, the palliation of debilitating symptoms is critically important in patient management. A multidisciplinary team consisting of representatives from surgery, medical oncology, gastroenterology, radiology, and palliative care medicine is essential for the optimal palliation of symptoms. In this article, the key issues in palliative care for patients with advanced pancreatic and biliary cancer are discussed. In particular, the prevention and amelioration of suffering due to obstructive jaundice, gastric outlet obstruction, cancer-related pain, pancreatic enzyme insufficiency, and thromboembolic disease is addressed. To this end, an algorithm for the multidisciplinary management of these challenging patients is proposed with the goal of providing clinicians with a useful framework for providing palliative care for patients with advanced pancreatic and biliary cancer.