Growth in knowledge about calcitonin gene-related peptide (CGRP) in the 
pathophysiology of migraine brought CGRP antagonism to headache medicine. 
Failures in development of small molecule CGRP receptor antagonists and 
increasing knowledge and use of monoclonal antibodies (mAbs) in medicine led to 
the breakthrough development of large molecule anti-CGRP mAbs: eptinezumab, 
erenumab, fremanezumab, and galcanezumab. This specifics about CGRP immunology 
aims to outline: (1) knowledge needed for CGRP antagonism and (2) developmental 
issues of specific CGRP antagonists for provider use. This clinically oriented 
review documents IgG structure and function; state of the art of monoclonal IgG 
production and ligand-antigen-antibodies in migraine therapeutics contributing 
to immunogenic risks and off-target toxicities. Specifics to CGRP ligand, 
receptor, antagonism, and molecules, small and large, complete this review. 
Completion will facilitate assessment of the similarities, differences, and 
application of the forthcoming anti-CGRP receptor and ligand antagonists for 
patients.