We reviewed studies concerning immunomodulating therapy in systemic sclerosis. These comprise mostly uncontrolled trials and case reports. Some of these studies hint at a possible beneficial effect of antimetabolites (azathioprine, 5-fluoro-uracil and methotrexate), cyclosporine and interferon-gamma. However, to give a clearcut answer on the efficacy of these drugs in systemic sclerosis, controlled studies are urgently needed.