The psychophysiological stress paradigm has been applied to detect pathways through which stress can induce migraine. We propose that the negative and inconsistent findings of previous studies can be ascribed to the restricted psychophysiological scope of these experiments, to insufficient operationalization of the concepts of stress, and to the lack of attention paid to the presence or absence of an attack after a stressful situation. Our present state of knowledge on the pathophysiology of migraine should form the basis for future psychophysiological research, which should focus on patients who are actually stressed and develop an attack afterwards.