Allogeneic hematopoietic SCT (HSCT) is an established treatment for some children with life-threatening hematological disease, immune deficiencies and inborn errors of metabolism. Despite advances in prevention and post transplant immuno-suppressive strategies, acute GvHD (aGvHD) remains a major cause of morbidity and mortality in children undergoing SCT. Although reported incidence rates differ, it has been estimated that, depending upon the patient and donor cohort studied, 20-50% of all transplanted patients will experience grade 2 or more aGvHD despite immuno-suppressive prophylaxis. aGvHD occurs when transplanted donor T lymphocytes recognize antigenic disparities between the host and recipient. Pathways other than direct T-cell-mediated cytotoxicity have been shown to be important in the pathogenesis. Inflammatory cytokine release has been implicated as the primary mediator of aGvHD and activation of T cells is one step in the complex process. Deregulated cytokine release by cells other than T cells leads to tissue damage associated with aGvHD. GvHD is a factor that compromises the overall success rate of allogeneic HSCT and remains a challenge, which, in turn, requires an understanding of the pathophysiology, clinical presentation and management of this complication. The authors concentrate on the most recent knowledge of the pathogenesis as well as the classification of aGvHD.