<p>The successes and failures of migraine pharmacotherapy since 1926, when H. W. Maier first successfully used ergotamine to relieve cerebral vasospasm in this disease that affects 15.2% of the world’s population, are reviewed. The discoverers of the 5-HT₃ receptor, whose followers failed in the use of tropisetron for the treatment of migraine, are reported. The development of the 5-HT_1B/1D receptor agonist sumatriptan and then other triptans is described. The drugs were declared the “gold standard” of migraine treatment but revealed not only the disadvantages of dihydroergotamine (insufficient efficacy and drug-abuse headache) but also contraindications for patients at risk of cardiovascular and cerebrovascular diseases. The problems with the use of triptans confirm the correctness of the antispasmodic approach to migraine pharmacotherapy by H. W. Maier and the view of the supporters of the hypotheses, i.e., vascular and cortical spreading depression in the first phase of the attack. Currently, painkillers that do not cause vasoconstriction, e.g., the 5-HT_1F receptor agonist lasmiditan and calcitonin gene-related peptide (CGRP) receptor antagonists, are used. At the same time, CGRP receptor antagonists also eliminate endogenous anti-ischemic protection of the brain and heart. The mechanism of the anti-migraine action of propranolol is discussed in detail. The 5-HT₂ receptor antagonist tropoxin and the anti-ischemic combination of a piperidine derivative with picamilon are proposed for the treatment of migraine. Despite the many drugs for the treatment of migraine, problems of the pathogenetic pharmacotherapy of migraine cannot be considered solved. Therefore, the search for a drug, i.e., the “gold standard,” should be continued.</p>