Stem cell therapy has shown promise in treating a variety of pathologies, such as myocardial infarction, ischaemic stroke and organ transplantation. The stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) axis plays a key role in stem cell mobilization. This review describes the important role of SDF-1 in tissue injury and how it works in tissue revascularization and regeneration via CXCR4. Furthermore, factors influencing the SDF-1/CXCR4 axis and its clinical potential in ischaemia reperfusion injury, such as renal transplantation, are discussed. Exploring signalling pathways of the SDF-1/CXCR4 axis will contribute to the development of stem cell therapy so that more clinical problems can be solved. Controlling directional homing of stem cells through the SDF-1/CXCR4 axis is key to improving the efficacy of stem cell therapy for tissue injury. CXCR4 antagonists may also be effective in increasing circulating levels of adult stem cells, thereby exerting beneficial effects on damaged or inflamed tissues in diseases that are currently not treated by standard approaches.