There is ample evidence for the influence of central nervous system modulation through inflammatory cellular reactions under psychosocial stress. These inflammatory reflexes might be of major influence not only for metabolic and vascular disease but also for many autoimmune diseases for which stress has been reported as a risk factor. In prospective trials on the influence of risk factors for the occurrence of cardiovascular events, both psychosocial stress and autonomic nervous control of the cardiovascular system were shown to have a major impact on event rates. The underlying cause of these findings seems to be explained in part by the direct influences of autonomic reflexes, potentially induced by psychosocial tasks, on the progression of atherosclerosis. Hence, future prospective studies that aim at deciphering the influence of chronic psychosocial stress and autonomic function on the pathogenesis of inflammatory and metabolic disease will need to include neurophysiologic, molecular, and clinical parameters. Because the neuroimmunologic axis can be seen as a system connecting mental states with inflammatory reactions, pro-inflammatory mediators and anti-inflammatory strategies should be studied as such in experimental settings.