Research into the pathogenesis of systemic sclerosis and other fibrotic conditions is becoming increasingly broad and sophisticated. In the past year, several provocative studies have presented evidence that autoantibodies may actually cause the vascular damage and fibrosis characteristic of systemic sclerosis. These autoantibodies include antiendothelial cell, antifibrillin-1, anti-matrix metalloproteinases 1 and 3, and antiplatelelet-derived growth factor beta, each having its own unique mechanism. Such reports provide novel avenues to pursue in understanding this enigmatic disease.