Hematopoietic stem cell transplantation (HSCT) represents a widely accepted therapeutic strategy for the treatment of hematologic disorders which are otherwise considered incurable. Alloreactive T cells infused with the stem cell inoculum may generate graft-versus-host disease (GVHD) representing one the most relevant obstacles to the successful outcome of patients receiving allogeneic HSCT. Areas covered: In this review, the authors provide an overview of the most recent approaches of T-cell depletion (TCD) including ex-vivo αβ+ TCD and in-vivo TCD with anti-thymocyte globulin (ATG). Expert opinion: Ex vivo depletion of donor T-cells prevents both acute and chronic GVHD without the need for any additional posttransplant immunological prophylaxis either in haploidentical HSCT and HLA matched transplants. Three prospective trials evaluating the efficacy of ATG in matched unrelated donor transplant recipients demonstrated that ATG reduces the incidence of both acute and chronic GVHD without a significant increase of relapse rate, and similar results have been reported in the setting of blood stem cell grafts from matched sibling donors VSports手机版. .