Circulating smooth muscle progenitor cells have been identified as a source for neointimal smooth muscle cells after various types of injuries to the vessel wall contributing to neointimal hyperplasia, implying a fundamental role of these progenitor cells in the vascular response to injury. Recent studies have provided insight into the molecular mechanisms of mobilization and local recruitment of smooth muscle progenitor cells. The CXC chemokine SDF-1alpha and its receptor CXCR4 have been identified as the central signaling axis regulating the homing of smooth muscle progenitor cells into the injured vessel wall. This review discusses the unique biologic functions of this chemokine and its contribution to stem-cell-based vascular repair and disease.