Enteroendocrine L cells are open-type enteroendocrine cells that play an important role in amino acid sensing. They detect amino acids by a number of membrane receptors such as calcium-sensing receptor and G protein coupled receptor family C group 6 subtype A. The receptors activate signaling pathways and trigger cellular electrical activities, inducing gut hormones secretion (glucagon-like peptide 1, glucagon-like peptide 2 and peptide YY). This review focuses on an array of findings on L cells as models, receptors and signaling pathways, electrical activities and hormones secretion in amino acid sensing. Several diseases that are closely related to L cells are also reviewed.