The observation that following stroke or peripheral nerve injuries the development of rheumatoid arthritis is either prevented or ameliorated in the affected limb was the first observation of the involvement of the neurological system in the pathogenesis of the disease. Much subsequent work has established that there are intimate and intricate associations between the central nervous system, the endocrine system and immuno-inflammatory mechanisms. The predominant interaction is through the hypothalamic-pituitary adrenal axis which mediates the secretion of corticotrophin releasing hormone which then stimulates the pituitary to release ACTH. A subsequent stimulation of the adrenal cortex leads to glucocorticoid release with their known potent anti-inflammatory effects. Many factors can interact within the central nervous system to modify this pathway. Of particular relevance is the observation that the hypothalamic-pituitary adrenal axis may be defective in rheumatoid arthritis. This has implications not only in terms of pathogenesis but also in the way in which glucocorticoids are used for the treatment of rheumatoid arthritis.