Cytokines are inducible, secretory proteins that mediate intercellular communication in the immune system. They are grouped in families referred as tumour necrosis factors, interleukins, interferons and colony stimulating factors. In recent years, it is clear that some of these proteins and their receptors are also produced in the central nervous system (CNS) by specific neural cell lineages under physiological and pathological conditions. The data we have hitherto let us suggest that cytokines play an important role in the regulation of both excitatory and inhibitory neurotransmission in the CNS. Growing evidence indicates that, in addition to the hormones of hypothalamic, pituitary and gonadal origin, autocrine/paracrine regulators play important roles in the reproductive functions. Cytokines, originally known as immunoregulatory proteins, may affect the neuroendocrine events of reproduction, ovarian/testis function, endometrium, the developing embryo, placenta and parturition. Cytokines can modulate and mediate the actions of hormones at their target cells and, in the opposite way, hormones may regulate the production and action of cytokines at three different levels: cytokine secretion, cytokine receptor expression and cellular responses. Cytokines may also function in an endocrine manner affecting distant targets. In addition, many cells in the reproductive system also produce cytokines independently of the presence of leukocytes, thus reproductive tissues are sites of cytokine action and production. There is compelling evidence that cytokines, in fact, play an important regulatory role in the development and normal function of ovarian and testicular tissues, and are surveyed as the important regulators of steroidogenesis and gamete production. Cytokines interfere with steroidogenesis at the level of testes, and ovaries. For instance, secretory products of macrophages are involved in the regulation of steroidogenesis, Sertoli cell activity, and germ cell survival in the human testes. In conclusion, cytokines interact with steroidogenesis in a systemic and complex manner, influencing development, function, and hormone production of the testes, and ovaries. Thus a variety of clinical situations may be due to cytokine action in the gonads. Therapeutic manipulation of the immune system may affect reproductive function. The aim of this chapter is to provide a summary of the extensive literature dealing with cytokines in central nervous system function, and gonadal biology, and to follow this with some speculation concerning the significance of these molecules in interactions between the immune system and the neuroendocrine system. This knowledge could be fundamental for the proposal of new therapeutic approaches to neurological, psychiatric and reproductive disorders. © 2014 by Nova Science Publishers, Inc. All rights reserved.