Oved Daniel, MD, Ramat Aviv Medical Center, Tel-Aviv, Israel, discusses whether CGRP treatments targeting the ligand or receptor are safer and more effective in migraine. Firstly, there are no clinical studies directly comparing erenumab, galcanezumab, and fremanezumab. This makes it difficult to compare between ligand and receptor CGRP treatments. Arguments supporting CGRP receptors include that erenumab, a CGRP receptor antagonist, is the only treatment with 3- and 5-year safety data and proven positive tolerability and efficacy profiles. Arguments supporting CGRP ligands suggest that targeting the CGRP receptor is insufficient. If targeting both the CGRP and amylin receptor is more efficacious than targeting the CGRP receptor alone, then perhaps targeting both the CGRP receptor and ligand will also be more effective. CGRP receptor antagonists are also associated with constipation, suggesting that targeting CGRP ligands is safer. This interview was conducted during the virtual 2021 World Congress on Controversies in Neurology (CONy) meeting.