Systemic sclerosis (SSc, scleroderma) is an often-fatal disease characterized by connective tissue fibrosis of skin and internal organs. In scleroderma, there is an excessive production and accumulation of extracellular matrix (ECM) components resulting from an increase in collagen synthesis and matrix stability. Understanding how this how excessive ECM is produced and remodeled may represent a novel therapeutic approach. In this review, the transcription factors and collagen-modifying enzymes underlying collagen overexpression and enhancing stability in SSc are discussed. Moreover, the role of matrix stiffness in promoting fibrosis via a feed-forward mechanism is discussed. Indeed, the emerging evidence is that enhanced ECM remodeling resulting in increased ECM stiffness may be sufficient in itself to sustain persistence fibrosis in SSc.