A growing body of evidence is shedding light on how vascular injury, tissue mononuclear cell infiltrates, and fibrogenesis are related in the pathogenesis of systemic sclerosis. Recent evidence points to a role for adhesion molecules in the binding of mononuclear leukocytes to endothelium and transvascular migration of these cells to connective tissue sites. Further interaction of mononuclear leukocyte integrins with connective tissue components at these sites leads to cytokine and growth factor release, resulting in upregulation of matrix production by fibroblasts and alterations of the fibroblast phenotype, leading to fibrogenesis.