The scleroderma (SSc) disease process involves dramatic dysfunction in acute and chronic vascular regulatory mechanisms; it presents initially with heightened vasoconstrictor or vasospastic activity and progresses to structural derangement or vasculopathy of the microcirculation. This article discusses the regulatory mechanisms that contribute to this dysfunction and the vascular changes in the context of the other aspects of the SSc disease process in a novel attempt to integrate the individual pathologies of the disease process.