Graft-versus-host-disease continues to be a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Gastrointestinal GVHD is the major cause of mortality. The initial phase of acute GVHD is triggered by tissue damage and associated loss of mucosal barrier function, primarily in the gastrointestinal tract, which is caused by the conditioning regimens needed to bring malignant disease to a minimal residual level suitable for subsequent immune control and to ablate existing immune function, allowing engraftment of the naïve donor inoculum. Stem cell transplantation typically uses total body irradiation, immunosuppression and chemotherapy to achieve these dual aims; however, they also result in damage to the GI tract mucosa and other cells contributing to the “cytokine storm”, which is characterized by the release of proinflammatory cytokines; classically Th1 cytokines: IFNγ, IL-2 and TNF-α and Th2 cytokines: IL-4, IL-5, IL-10 and IL-13. Current mainstay GVHD therapies focus on broad immunosuppression, which can affect engraftment and, in some contexts, reduce the desired graft-versus-tumor activity. A reduction in the bacterial burden by use of antimicrobial decontamination in the posttransplant period can reduce GVHD severity. The lung and the skin are the primary target organs in chronic GVHD, manifesting as fibrosis - bronchiolitis obliterans and scleroderma. Acute GVHD remains a major cause of treatment failure resulting in mortality in 20% of recipients and 60-80% of survivors experience some degree of chronic GVHD.