Migraine has been endemic for many centuries. Seamlessness between plant-derived and synthetic migraine therapies is evident in three major aspects: (A) The latter are molecular adaptations of the former, (B) Combinations of herbal and non-herbal migraine therapies (e.g., one for prophylaxis and the other for acute therapy) are used by many patients, and (C) All migraine treatments, whether plant-derived or not, are capable of clinical trial using the same endpoints. At least two, newly discovered plant-derived migraine therapies are currently under research using standard clinical trial methodology. Suggestions are provided for more flexible clinical trial designs that might particularly suit research into herbal remedies. The future of migraine therapy is likely to continue to exhibit an intimate, symbiotic relationship between plant-derived and synthetic drugs.