The gastroenterologist, when performing an esophagogastroduodenoscopy, is the only medical care provider with easy access to the duodenum. This simple fact is pivotal in this article that discusses why the duodenum has become such an important anatomic region of interest. Recent insights have revealed the critical physiologic and pathophysiologic role of the small bowel in metabolic homeostasis and its potential role as a driver of obesity, insulin resistance, and subsequent type 2 diabetes mellitus (T2DM).