Vascular endothelial injury in systemic sclerosis (SSc) includes a spectrum of changes that involve predominantly the microcirculation and arterioles. The pathologic changes in the blood vessels adversely impact the physiology of many organ systems, with a reduction in the size of microvascular beds leading to decreased organ blood flow and ultimately to a state of chronic ischemia. Current hypotheses in SSc vascular disease suggest a possible chemical or infectious trigger.