The analysis and understanding of the complex effects of endocrine and nervous system alterations on the inflammatory process in human arthritis is far from complete. Such alterations are observed as decreased responsiveness of the hypothalamic-pituitary-adrenal axis, an inadequate production of cortisol in relation to inflammation, and - consequently - elevated sympathetic activity, alterations of sex hormone metabolism (loss of androgens), psychological alterations (with chronic fatigue and symptoms of depression due to elevated circulating cytokines), local reduction of synovial sympathetic innervation, altered metabolism of estrogens in the synovium, and high expression of estrogen receptors in synovial cells. An understanding of these alterations will help to identify the different neuroendocrine immune mechanisms involved in the pathophysiology of rheumatoid arthritis and could trigger research into novel therapeutic targets for the treatment of patients with rheumatoid arthritis.