Recent studies have provided further evidence that hypothalamic-pituitary-adrenal axis disturbance is central to the pathophysiology of depression. Evidence continues to emerge that supports the view that the hypothalamic-pituitary-adrenal axis is an appropriate target for the development of novel antidepressants, and that disturbances in the release of growth hormone in depression are secondary to an alteration in the hypothalamic-pituitary-adrenal axis. Studies that focus on blunted 5-hydroxytryptamine-stimulated prolactin release have indicated that it is a marker for aggression rather than the core symptoms of depression. Until recently, few studies focused on bipolar patients. This situation has now altered and our biological understanding of bipolar illness is expanding.