Glucagon-like peptide-1 (GLP-1) is a key incretin peptide that promotes insulin secretion in response to nutrient ingestion, but also has a range of other actions including preservation of b-cell mass, reduction in gastric emptying and reduction in appetite that make it a desirable target for treatment of type II diabetes. GLP-1 exerts its effects by binding to the GLP-1 receptor (GLP-1R), a Class B G protein-coupled receptor (GPCR). In recent years, it has become clear that individual GPCRs can exist in multiple receptor conformations and can elicit numerous functional responses, both G protein- and non-G protein-mediated. This has led to the discovery that different ligands can stabilize distinct subsets of receptor conformations that can “traffic” stimulus to diverse functional outputs with varying prominence, a concept referred to as biased agonism (also known as functional selectivity, stimulus bias or ligand-directed signaling). I will discuss the concept of ligand-directed signal bias as it applies to the GLP-1 receptor, new information on peptide interactions with the receptor drive signal bias and the implications of this for development of drugs that target the GLP-1 receptor.