In 1949 Hench and co-workers reported beneficial effects of cortisone treatment of patients with rheumatoid arthritis. The results of these clinical trials were so dramatic that clinicians soon used glucocorticoids to treat other diseases. Symptomatic improvement was reported only in certain cases. Some other conditions in which glucocorticoid therapy is now used are adrenal insufficiency, rheumatic carditis, nephrotic syndrome, systemic lupus erythematosis, bronchial asthma, dermatitis, psoriasis, chronic ulcerative colitis and leukemia.The clinical use of glucocorticoids resulted in the development of synthetic glucocorticoids which possessed more of the anti-inflammatory activity of cortisone and less of the salt retaining property of this corticosteroid. These new synthetic glucocorticoids, especially the fluorinated ones, unfortunately possessed many untoward side effects observed with cortisone. The purpose of this review is to discuss studies which demonstrate that glucocorticoids decrease collagen synthesis in vivo and in cell culture and which may explain the adverse effect these steroids have on connective tissues. Furthermore, some of the studies presented indicate that glucocorticoids selectively decrease collagen synthesis.