The pathogenetic role of autoantibodies in systemic sclerosis (SSc) remains unclear, but these autoantibodies have been established as strong predictors of disease outcome and the pattern of organ complications in patients with this condition. The three most frequently observed types of SSc-specific autoantibody-anti-centromere antibodies, anti-topoisomerase antibodies and anti-RNA polymerase III antibodies-are found in over 50% of patients; the presence of each is generally exclusive of the others. Although a lot less frequently observed, antibodies directed against U3RNP and Th/To are also specific for scleroderma, whereas anti-Pm/Scl, anti-Ku and anti-U1RNP antibodies are seen mainly in patients with overlap syndromes. Up to 11% of patients with SSc can test negative for antinuclear antibodies. Strong links exist between autoantibody specificities and disease presentation and outcome, which make autoantibodies essential assessment tools in patients with SSc.