In the past 40 years, considerable advances have been made in the field of neuroendocrinology, highlighting the etiopathogenic significance of endocrine systems in mood disorders. More recently, the hypothalamic-pituitary-adrenal (HPA) axis has been the focus of research investigating the pathogenesis of bipolar disorder. Novel,therapeutic approaches targeting the HPA axis have also evolved. This article focuses specifically on the role of the HPA axis in bipolar disorder.