This article reviews recent developments in cytokine research that pertain to pharmacological treatment of mood disorders such as antidepressants and lithium. We review the possible involvement of cytokines in mood disorders and their role in the therapeutic effects of antidepressant drugs. Growing evidence suggests that specific cytokines signal the brain to generate neurochemical, neuroimmune, neuroendocrine and behavior changes. An imbalance of cytokines within the central nervous system (CNS), or even systemically, may play a role in the pathophysiology of mood disorders. Modulation of these cytokines by chronic antidepressant treatment may result in restored balance. However, the effect of antidepressants on cytokines is still unclear both in clinical and preclinical research due to limited data. Further research is needed to clarify the involvement of cytokines in mood disorders. Understanding this relationship may lead to rational, therapeutic improvements in antidepressant and mood stabilizing drugs.