Great advances have been made in our understanding of Takotsubo syndrome in the past decade, but the aetiology of the condition remains incompletely understood. The most established theory, that catecholamine-mediated myocardial stunning is provoked by emotional or physiological stress, is supported by the presence of supraphysiological levels of plasma catecholamines in patients with Takotsubo syndrome. For this reason, the hyperexcitability of the autonomic nervous system under conditions of physical and emotional stress is often assessed in these patients. Observational studies have indicated that a predisposing influence of chronic or traumatic stress, anxiodepressive disorders, and maladaptive personality traits are linked to the pathogenesis of Takotsubo syndrome. Chronic stress can influence autonomic function through dysregulation of the hypothalamic-pituitary-adrenal axis and contribute to the development of cardiovascular disorders. In this Perspectives article, we discuss the current knowledge of the psychoneuroendocrinological and psychosocial mechanisms underlying the pathophysiology of Takotsubo syndrome.