Glucagon-like peptide-1 (GLP-1) is released in response to meals and exerts important roles in the maintenance of normal glucose homeostasis. GLP-1 is also important in the regulation of neurologic and cognitive functions. These actions are mediated via neurons in the nucleus of the solitary tract that project to multiple regions expressing GLP-1 receptors (GLP-1Rs). Treatment with GLP-1R agonists (GLP-1-RAs) reduces ischemia-induced hyperactivity, oxidative stress, neuronal damage and apoptosis, cerebral infarct volume, and neurologic damage, after cerebral ischemia, in experimental models. Ongoing human trials report a neuroprotective effect of GLP-1-RAs in Alzheimer's and Parkinson's disease. In this review, we discuss the role of GLP-1 and GLP-1-RAs in the nervous system with focus on GLP-1 actions on appetite regulation, glucose homeostasis, and neuroprotection.