Despite the large body of scientific data, there remains a number of open questions concerning their effect in subtypes of migraine, predictors of (in)efficacy, long term management strategies, combination with other treatments, cost-effectiveness, effect in other headache types and, given the known myriad of physiological actions of CGRP, the potential adverse effects and possible contraindications due to its blockade in the long term. This evidence concerns the gene CALCA and migraine disorder.