Systemic scleroderma is characterized by a chronic inflammatory process of unknown etiology resulting in an increased deposition of connective tissue proteins in the involved organs. Involvement of the vascular system and the resulting fibrosis lead to atrophy and malfunction of the involved internal organs and the skin. Due to the development of new therapeutic concepts in particular with regard to the vascular involvement, the interaction between the vascular system and the connective tissue moves increasingly into focus. This review describes the major advancemades during recent years for the understanding of the pathophysiology of systemic scleroderma.