There is an increasingly impressive database concerning the possible involvement of cytokines in depression and their role in the therapeutic effects of antidepressants. Based on the discussions which took place on these issues at a recent meeting held in Roscoff, France, this perspective summarizes in a critical way the evidence in favor of such a possibility, and points out the needs for further research to clarify both the nature of the subtle dysregulations that affect neuroendocrine-immune interactions in depressive disorders and their contribution to psychopathology.