The hypothesis postulates that a brief episode of focal cerebral hypoxia occurs in every attack of migraine. Clinical biochemical and technical (EEG and CT scans) evidence is summarized suggesting that cerebral hypoxia is seen as the turning-point in the pathogenesis of the attack. It may be provoked by different mechanisms in different patients; the potential role of decreased oxygen supply and of increased oxygen need are reviewed and excess sympathetic drive is considered a potential key mechanism in a majority of patients. Whether or not focal hypoxia leads to a genuine migraine attack, depends largely upon the quality of the whirlpool of biochemical, vascular and hematological changes that follow the hypoxic episode. These changes are discussed and it is concluded that those which have been reported to occur during migraine attacks could be due to a preceding hypoxic event. Finally, the hypoxia viewpoint is confronted with some popular theories about the pathogenesis of migraine. It is found that the other points of view are compatible with the hypoxia hypothesis.