The current issue of Acta Neuropsychiatrica presents a series of papers which together provide a broad overview relating stress, immunity, cytokine activity and depressive illness, as well as the influence of cytokines on other neurological disorders. This introduction to the issue presents a broad perspective of the impact of stressors on immune functioning in animal studies and in humans, considering the potential effects of acute, subchronic and chronic stressors, as well as the contribution of previous stressor experience in promoting neurochemical and immunological alterations. Given the supposition that cytokines may act as immunotransmitters, and immune challenge may be viewed as a stressor, a brief review is provided concerning the impact of stressors and cytokine challenges on central neurochemical functioning, with particular emphasis on the commonalties between the effects of these treatments. It is suggested that by virtue of the neurochemical changes imparted by cytokines, a depressive affect may be instigated, just as it is in response to psychogenic stressors. To this end, an overview is presented concerning the relationship between cytokines and depression, as well as the influence of cytokine treatments on behavioral changes in animal studies and among patients receiving immunotherapy. Provisionally, the data support the view that activation of the inflammatory response system may contribute to affective illness, and that cytokines may act as signaling molecules to activate central nervous system processes regulating mood states.