Much progress has been made in the understanding of the impact of the neuroendocrine immune interactions and the pathogenic role in systemic lupus erythematosus, clinically and at the molecular level. This article focuses on the intertwining networks that involve the hypothalamic-pituitary-adrenal axis, cytokines within the central nervous system, and the sympathetic system. Hormones (estrogen, prolactin, gonadotropin-releasing hormone, and leptin) play an important role as immunomodulatory agents.