The relationship between prolactin and the immune system has been demonstrated in the last two decades, opening new windows in the field of the immunoendocrinology. Prolactin has an important role in the innate and adaptive immune response. Increased prolactin levels have been described in autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, and systemic sclerosis among others. Hyperprolactinemia is associated with active disease and organ involvement in systemic lupus erythematosus. Therefore, prolactin is an integral member of the immunoneuroendocrinology network and seems to have a role in pathogenesis of autoimmune diseases. Few controlled studies of dopamine agonist treatment in humans with autoimmune disease have been conducted only in systemic lupus erythematosus patients, which support the potential efficacy of such agents even during pregnancy and postpartum. Further studies are necessary to elucidate the mechanisms by which prolactin affects autoimmune disease activity, increase the inflammatory mechanism, and determine the role of anti-prolactinemic drugs to regulate the immune/inflammatory process.