Multiple peptide hormones produced within the gastrointestinal system aid in the regulation of energy homeostasis and metabolism. Among these is the intestinotrophic peptide glucagon-like peptide-2 (GLP-2), which is released following food intake and plays a significant role in the adaptive regulation of bowel mass and mucosal integrity. The discovery of GLP-2's potent growth-promoting and cytoprotective effects in the gastrointestinal (GI) tract stimulated interest in its use as a therapeutic agent for the treatment of GI diseases involving malabsorption, inflammation, and/or mucosal damage. Current research has focused on determining the physiological mechanisms contributing to the effects of GLP-2 and factors regulating its biological mechanisms of action. This chapter provides an overview of the biology of GLP-2 with a focus on the most recent findings on the role of this peptide hormone in the normal and diseased GI tract.