Ampullary neoplasms are largely uncommon and benign neoplasms are managed either by endosocopic resection or surgery. Endoscopy has been helpful in detecting ampullary neoplasms, their extent, and surveillance. Endoscopic papillectomy offers a curative option for ampullary neoplasms. On the other hand, only 15% of pancreatic neoplasms can be managed with curative intent, while majority of them are managed palliatively because of their late presentation and presence of fewer therapeutic options. Endoscopy is helpful in the successful drainage of the biliary system as well as pain management. Celiac plexus block (CPB) and neurolysis have emerged as a tool for pain relief by disrupting the pancreatic afferent signaling to the spinal cord in an attempt to reduce abdominal pain and improvement in the patient’s quality of life. Obstructive jaundice is the most common symptom caused by pancreatic cancer, occurring in approximately 70–80% of patients at the time of diagnosis; endoscopic approaches have proved to be safe and effective for biliary drainage (BD) in such situations. The traditional approach for the palliation of malignant gastric outlet obstruction (GOO) has been gastrojejunostomy; however, endoscopic self-expandable metal stent (SEMS) placement has become more routine in recent times.