Relapse remains the worst life-threatening complications after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with acute myeloid leukemia(AML),whose prognosis has been historically dismal.Given the rapid development of genomics and immunotherapies,the interfer-ence strategies for AML recurrence have been changing these years.More and more novel targeting agents that have received the U.S.Food and Drug Administration(FDA)approval for de novo AML treat-ment have been administrated in the salvage or maintenance therapy of post-HSCT relapse.Targeted stra-tegies that regulate the immune microenvironment of and optimize the graft versus leukemia(GVL)effect of immune cells are gradually improved.Such agents not only have been proven to achieve clinical benefits from a single drug,but if combined with classic therapies,can significantly improve the poor prognosis of AML patients who relapse after allo-HSCT.This review will focus on currently available and promising upcoming agents and also discuss the challenges and limitations of targeted therapies in the allogeneic hematopoietic stem cell transplantation community.