The duodenum, the initial segment of the small intestine, is divided into four parts: the superior (D1), descending (second) (D2), horizontal (D3), and ascending (D4) segments. Despite its short length, the descending part (D2 segment) holds clinical significance due to its anatomical proximity to structures such as the gallbladder, right kidney, colon, and pancreas. This anatomical localization and contiguity give rise to various pathologies, including congenital, inflammatory, infectious, neoplastic, vascular, and traumatic conditions. Cross-sectional imaging modalities play a pivotal role in evaluating pathologies of the second (D2) segment of the duodenum. This article aims to provide a comprehensive overview of these pathologies and delineate their imaging characteristics.