Reduced-intensity hematopoietic stem cell transplantation (RIST) is a new approach of stem cell transplantation, which has shown promising features as reported in multiple phase I and II studies. Elderly patients, who are not eligible for conventional myeloablative hematopoietic stem cell transplantation (HSCT), are now treatable with RIST. It has also reduced regimen-related toxicity and provided better prognosis in short-term follow-up than that of conventional HSCT. Favorable results have been reported particularly in hematological malignancies, such as chronic myelocytic leukemia and malignant lymphoma. Among solid tumors, metastatic renal cell carcinoma was found to respond well to RIST. Clinical studies are currently being conducted to evaluate the efficacy of RIST in other types of solid tumors. However, the mechanism of graft-versus-host disease and graft-versus-tumor remains unclear. More knowledge on the mechanism is crucial to enhance antitumor effect and to further improve the prognosis.