Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the major curative treatment for patients with malignant hematologic diseases. However, a number of serious complications limits successful outcomes. Acute graft-versus-host disease(GVHD) is a major cause of death following allo-HSCT.The mortality rate is 50 % in Ⅱ -Ⅳ aGVHD. At present, the major prevention methods conclude inhibiting T cell activation and proliferation, depleting of T cell in graft, and decreasing the dose of preconditioning. And only one quarter of these patients will have a complete response to first-line corticosteroid therapy. Patients with steroid resistant acute GVHD require second-line therapy to which the response rate is only 30 %-50 %.Second-line therapies including monoclone antibody, chemotherapy and cytokine inhibitor were used. Secondline options can impair immune reconstitution and increase the risk for infection. Therefore, novel approaches to prevent and treat GVHD are critically needed. This work will review novel immuno-modulatory therapy currently being employed both for the prevention and treatment of GVHD.