The importance of the hypothalamic-pituitary-adrenalaxis (HPA) for the regulation of immunological functions has been greatly appreciated in the past (1-3). Activation of the HPA axis due to a given stimulus leads to a stress response which modulates the immune response. The interactions between the immune system and HPA-axis may be characterized by a circuit which includes I) activation of the HPA-axis and initiation of the stress response which, in term, has immune-modulating properties; II) a feedback mechanism derived from the immune system which regulates the HPA-axis. Current concepts on these regulatory circuits mainly favor the action of cytokines as mediators of the immune-endocrine regulation circuits which have been shown to interfere with the endocrine system on all levels of the HPA-axis. Over the past few years, it has become evident that the adrenal gland, itself, as the main effector organ of the HPA-axis, is a major site for both synthesis and action of numerous cytokines. This review summarizes current knowledge on production, action, as well as functional implications of cytokine action within the adrenal gland during development, health and disease.