Many lines of research have established the numerous routes by which the immune and central nervous systems (CNS) communicate. The CNS signals the immune system via hormonal and neuronal pathways and the immune system signals the CNS through similar routes via immune mediators and cytokines. The primary hormonal pathway by which the CNS regulates the immune system is the hypothalamic-pituitary-adrenal (HPA) axis, through the hormones of the neuroendocrine stress response. The sympathetic nervous system regulates immune system function primarily via adrenergic neurotransmitters released through neuronal routes. Neuroendocrine regulation of immune function is essential for survival during stress or infection and to modulate immune responses in inflammatory disease. Glucocorticoids are the main effector endpoint of the neuroendocrine response system.