Circulating antinuclear autoantibodies contribute to the diagnosis of systemic sclerosis (SSc) and correlate with disease-specific organ manifestations. Recent findings show the induction of interstitial lung disease and obliterative vasculopathy by transfer of IgG from SSc patients in healthy mice indicating a contribution of antibodies to SSc pathogenesis. Several functional or agonistic autoantibodies have been described in SSc, thus putting autoimmunity into a new spotlight. Autoantibodies against the angiotensin II receptor type-1 and the endothelin1 receptor type-A are associated with severe disease and provide new insights into its pathogenesis. They link the hallmarks of SSc, vasculopathy, immune activation, and fibrosis. At present, the contribution of the specific antibodies to disease manifestations remains to be examined. However; functional autoantibodies could represent a significant piece in the puzzle of SSc pathogenesis and may open new gateways and opportunities for therapeutic intervention. This review focuses on the features of functional autoantibodies in SSc.