Systemic sclerosis is the most severe of all connective tissue diseases. The distinctive pathogenic process involves sequential or concomitant abnormalities in blood vessel function, immunity and, ultimately, fibroblast function. These specific characteristics may explain the results of treatment evaluations. The decrease in excess mortality shown in recent studies seems chiefly ascribable to the use of cardiovascular drugs. Angiotensin-converting enzyme (ACE) inhibitors are effective in resolving renal crisis, prostacyclins and endothelin antagonists improve pulmonary hypertension, and calcium antagonists and ACE inhibitors benefit patients with myocardial involvement. On the other hand, immunomodulatory drugs and other agents investigated for their disease-modifying potential failed to influence skin fibrosis in controlled trials. Trials of immunosuppressants are ongoing. Available results indicate that emphasis should be put on cardiovascular drugs. The development of criteria for disease activity and severity would facilitate future research on the treatment of systemic sclerosis.