Systemic sclerosis is a rare chronic disease with inflammatory and vascular features leading to increased fibrosis of skin and internal organs. The pathogenesis of systemic sclerosis and scleroderma like diseases appears to be influenced rather by environmental than by genetic factors. Clinical and pathogenetic aspects of systemic sclerosis show similarities to untreated chronic graft-versus-host-disease after bone marrow transplantation. New insights into the pathogenesis of systemic sclerosis give reason to hope that better therapeutic approaches will be developed in the future.