There is growing evidence that cytokines are responsible for several important aspects of brain functioning, including neuroendocrinological, neuroimmune and behavioural regulation. In the context of depression, cytokines are divided into pro-inflammatory and anti-inflammatory groups, while some pro-inflammatory cytokines are associated with increased activity of the hypothalamic-pituitaryadrenal axis and, particularly, with rise in the adrenocorticotropic hormone and cortisol levels. It has also been reported that pro-inflammatory cytokines may stimulate serotonin reuptake and decrease the synthesis of serotonin by influencing indoleamine 2,3-dioxygenase enzyme. This is in good line with clinical evidence demonstrating high prevalence of depressive symptoms (e.g. fatigue, dysphoria, loss of interest, anorexia, psychomotor retardation, and fever) among patients with cancer or hepatitis-C who are receiving cytokine based immunotherapy. These symptoms are k now n to be targeted and quite successfully resolved by antidepressant medications. Furthermore, the cytokine hypothesis of depression proposes that immunological disturbances may cause significant deterioration in mood through affecting certain neurotransmitters in the central neural system, including serotonin. However, relevant available data are still conflicting. There is also well recognized opinion that different neuroimmunological mechanisms may underlie different subtypes of depression, for example, melancholic versus non-melancholic or atypical depression. On the other hand, the effect of antidepressant medications on immune activation may vary in different ways and depend on their pharmacological properties. Some preliminary reports have also demonstrated that treatment response to antidepressants could be predicted by levels of certain cytokines.