The immune system is still regarded by many as autonomous and prolactin (Prl) has traditionally been considered as a lactogenic hormone. However, experimental, clinical and epidemiological data suggested that hyperprolactinemia constitutes a risk for the development of autoimmunity. Elevated serum levels of Prl in adjuvant arthritis, collagen type II-induced arthritis, systemic lupus erythematosus (SLE) and autoimmune type I diabetes mellitus influenced the outcome of these diseases. In human SLE, Prl favors the production of anti-double stranded (ds) DNA. While glucocorticoids would damp the immune reactivity, Prl constitutes a stimulatory link between the neuroendocrine and immune systems. Accordingly, in rodents and humans, the suppression of Prl release with Bromcriptine treatment is associated with decreased disease activity score and transient suppression of anti-ds DNA. Furthermore, combination therapy with Cyclosporine A (CsA) or other anti-inflammatory drugs can result in synergistic effects. Further directions include the potential “direct” effect of Bromocriptine on the immune system and the nature of its synergy with CsA.