This review considers the similarities and differences between the physiological systems regulated by gut-derived and neuronally-produced GLP-1. It addresses the questions of whether peripheral and central GLP-1 sources constitute separate, linked, or redundant systems, whether the brain GLP-1 system consists of disparate sections or is a homogenous entity, and it explores the implications of the answers to these questions for the use of GLP-1 receptor agonists as anti-obesity drugs.