Scleroderma or systemic sclerosis (SSc) is a complex disease characterized by vasculopathy and deregulated immune and fibroblast activation. The resulting excessive production of collagens and other extracellular matrix proteins by fibroblasts as well as the inflammatory response leads to the development of scleroderma. Recently, some emerging data have been showing a possible link between the type I and II interferons (IFNs) and SSc pathogenesis. IFNs are well-known immunomodulators and inhibitors of collagen production. However, IFN therapy also has been implicated in the development or exacerbation of several autoimmune diseases, including SSc. Some studies also showed an increase mRNA and protein levels of IFNs and several interferon stimulated genes in cells and tissues from SSc patients. In this review we discuss about a possible role for IFNs in SSc development and pathogenesis.