Stromal cell-derived factor-1 was originally found as a chemoattractant for immune cells. Later it was shown that stromal cell-derived factor-1 and its specific receptor CXCR4 were widely expressed in the developing and mature brains. They participate in a variety of physiological and pathological processes including brain development, angiogenesis, neurodegeneration and neurogenesis. Stromal cell-derived factor-1/CXCR4 plays a particularly important role in adult neurogenesis through mediating the proliferation of neurogenitors, regulating the migration, differentiation, as well as functional integration of newborn neurons into existing networks. After stroke, adult neurogenesis in both the subventricular zone and subgranular zone is robustly increased and stromal cell-derived factor-1 and matrix metalloproteinases are released by damaged tissue. Stromal cell-derived factor-1 promotes the proliferation of neuroblasts and their migration to injured areas. However, the majority of the neuroblasts produced after stroke undergo apoptosis and only a few differentiate and survive in the long-term. The interaction of stromal cell-derived factor-1 and matrix' metalloproteinases may contribute to the unfavorable local microenvironment diminishing the survival of newborn neurons. Stromal cell-derived factor-1/matrix metalloproteinases and their downstream pathways may provide a new target for the treatment of stroke.