The digestive system is endowed with its own, local nervous system, referred to as the enteric nervous system (ENS). Given the varied functions of small intestine, its ENS has developed individualized characteristics relating to motility, secretion, digestion, and inflammation. The ENS regulates the major enteric processes such as immune response, detecting nutrients, motility, microvascular circulation, intestinal barrier function, and epithelial secretion of fluids, ions, and bioactive peptides. Remarkable progress has been made in understanding the signaling pathways in this complex system and how they work. In this article, we focus on recent advances that have led to new insights into small intestinal ENS function and the development of new therapies.