A growing body of evidence demonstrates the role of gut-derived hormones in the control of energy homeostasis. Among those intestinal signals, physiological and therapeutic interest has been drawn to glucagon-like peptide-1 (GLP-1). The main reasons are that this hormone 1) is secreted by epithelial intestinal L-cells in response to glucose and lipids, 2) enhances glucose-stimulated insulin secretion, 3) improves blood glucose profiles of type 2 diabetic patients by means of several actions on pancreatic hormone secretions, 4) reduces body weight and food intake, and 5) slows gastric emptying. Furthermore, recent evidence has suggested that the nervous system is a key player accounting for the beneficial role of GLP-1 on the control of energy homeostasis. Hence, the role of GLP-1 on the gut-to-brain axis is reviewed.