Periampullary pathologies are the lesions found within 2 cm of the ampulla. The periampullary region is a small yet complex anatomical structure. It includes the ampulla itself, the second part of the duodenum, the distal-most portion of the common bile duct, and the head of the pancreas. The abnormalities in this region pose various challenges in terms of diagnosis as well as treatment. Hence to evaluate and characterize a disease process in this area, a thorough knowledge of the relevant imaging anatomy and various imaging appearances, along with a systematic step-wise approach, is needed.