Pancreatic cancer is an aggressive malignancy, and the current 5-year survival rate in the United States, according to the Surveillance, Epidemiology, and End Results Program data, approximates 12%. Although the current standard for resectable pancreatic cancer most commonly includes neoadjuvant chemotherapy prior to a curative resection, surgery in the majority of patients has historically been palliative. The latter interventions include open or laparoscopic bypass of the bile duct or stomach in cases of obstructive jaundice or gastric outlet obstruction, respectively. Non-surgical interventional therapies started with percutaneous transhepatic biliary drainage (PTBD), both as a palliative maneuver in unresectable patients with obstructive jaundice and to improve liver functions in patients in whom surgery was delayed. Likewise, interventional radiologic techniques included placement of plastic and ultimately self-expandable metal stents (SEMS) through PTBD tracts in patients unresectable for cure as well as percutaneous cholecystostomy in patients who developed cholecystitis in the context of malignant obstructive jaundice. Endoscopic retrograde cholangiopancreatography (ERCP) and stent placement (plastic/SEMS) was subsequently used both preoperatively and palliatively, and this was followed by, or undertaken in conjunction with, endoscopic gastro-duodenal SEMS placement for gastric outlet obstruction. Although endoscopic ultrasound (EUS) was initially used to cytologically diagnose and stage pancreatic cancer, early palliation included celiac block or ablation for intractable pain. However, it took the development of lumen-apposing metal stents (LAMS) to facilitate a myriad of palliative procedures: Cholecystoduodenal, choledochoduodenal, gastrohepatic and gastroenteric anastomoses for cholecystitis, obstructive jaundice, and gastric outlet obstruction, respectively. In this review, we synopse these procedures which have variably supplanted surgery for the palliation of pancreatic cancer in this rapidly evolving field.