Systemic sclerosis (scleroderma; SSc) is an autoimmune disorder of unknown etiology characterized by severe and progressive cutaneous and visceral fibrosis, pronounced alterations in the microvasculature, and numerous cellular and humoral immunological abnormalities. Clinically, systemic sclerosis is very heterogeneous, ranging from mild limited forms of skin sclerosis (LcSSc) with minimal internal organ involvement to severe skin to multiple internal organ fibrosis and extensive skin fibrosis (DcSSc). Mortality and morbidity in systemic sclerosis is very high and are directly related to the extent of the fibrotic and microvascular alterations. The interactions between blood vessels, fibroblast activity, and immunological processes play an important role in the pathogenesis of SSc.