Acute and chronic graft-versus-host disease (GVHD) develop in a significant proportion of transplant recipients and still represent one of the major causes of morbidity and mortality after allogeneic BMT. Prevention of GVHD does not only attempt to reduce acute toxicity and morbidity of transplantation but also to ameliorate long term outcome. GVHD is a T-cell mediated disease affecting multiple target organ systems. Recent research has tremendously improved our understanding of the pathophysiology of the disease. These new data are reviewed with main emphasis on their impact for children. The most important task for the future will be to make these new strategies fruitful for clinical application.